Добірка наукової літератури з теми "LHCSR1"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся зі списками актуальних статей, книг, дисертацій, тез та інших наукових джерел на тему "LHCSR1".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Статті в журналах з теми "LHCSR1"
1
Girolomoni, Laura, Stefano Cazzaniga, Alberta Pinnola, Federico Perozeni, Matteo Ballottari, and Roberto Bassi. "LHCSR3 is a nonphotochemical quencher of both photosystems inChlamydomonas reinhardtii." Proceedings of the National Academy of Sciences 116, no. 10 (February 19, 2019): 4212–17. http://dx.doi.org/10.1073/pnas.1809812116.
Повний текст джерелаАнотація:
Photosynthetic organisms prevent oxidative stress from light energy absorbed in excess through several photoprotective mechanisms. A major component is thermal dissipation of chlorophyll singlet excited states and is called nonphotochemical quenching (NPQ). NPQ is catalyzed in green algae by protein subunits called LHCSRs (Light Harvesting Complex Stress Related), homologous to the Light Harvesting Complexes (LHC), constituting the antenna system of both photosystem I (PSI) and PSII. We investigated the role of LHCSR1 and LHCSR3 in NPQ activation to verify whether these proteins are involved in thermal dissipation of PSI excitation energy, in addition to their well-known effect on PSII. To this aim, we measured the fluorescence emitted at 77 K by whole cells in a quenched or unquenched state, using green fluorescence protein as the internal standard. We show that NPQ activation by high light treatment inChlamydomonas reinhardtiileads to energy quenching in both PSI and PSII antenna systems. By analyzing quenching properties of mutants affected on the expression of LHCSR1 or LHCSR3 gene products and/or state 1–state 2 transitions or zeaxanthin accumulation, namely,npq4,stt7,stt7 npq4,npq4 lhcsr1,lhcsr3-complementednpq4 lhcsr1andnpq1, we showed that PSI undergoes NPQ through quenching of the associated LHCII antenna. This quenching event is fast-reversible on switching the light off, is mainly related to LHCSR3 activity, and is dependent on thylakoid luminal pH. Moreover, PSI quenching could also be observed in the absence of zeaxanthin or STT7 kinase activity.
2
Kosuge, Kotaro, Ryutaro Tokutsu, Eunchul Kim, Seiji Akimoto, Makio Yokono, Yoshifumi Ueno, and Jun Minagawa. "LHCSR1-dependent fluorescence quenching is mediated by excitation energy transfer from LHCII to photosystem I in Chlamydomonas reinhardtii." Proceedings of the National Academy of Sciences 115, no. 14 (March 19, 2018): 3722–27. http://dx.doi.org/10.1073/pnas.1720574115.
Повний текст джерелаАнотація:
Photosynthetic organisms are frequently exposed to light intensities that surpass the photosynthetic electron transport capacity. Under these conditions, the excess absorbed energy can be transferred from excited chlorophyll in the triplet state (3Chl*) to molecular O2, which leads to the production of harmful reactive oxygen species. To avoid this photooxidative stress, photosynthetic organisms must respond to excess light. In the green alga Chlamydomonas reinhardtii, the fastest response to high light is nonphotochemical quenching, a process that allows safe dissipation of the excess energy as heat. The two proteins, UV-inducible LHCSR1 and blue light-inducible LHCSR3, appear to be responsible for this function. While the LHCSR3 protein has been intensively studied, the role of LHCSR1 has been only partially elucidated. To investigate the molecular functions of LHCSR1 in C. reinhardtii, we performed biochemical and spectroscopic experiments and found that the protein mediates excitation energy transfer from light-harvesting complexes for Photosystem II (LHCII) to Photosystem I (PSI), rather than Photosystem II, at a low pH. This altered excitation transfer allows remarkable fluorescence quenching under high light. Our findings suggest that there is a PSI-dependent photoprotection mechanism that is facilitated by LHCSR1.
3
Roach, Thomas. "LHCSR3-Type NPQ Prevents Photoinhibition and Slowed Growth under Fluctuating Light in Chlamydomonas reinhardtii." Plants 9, no. 11 (November 18, 2020): 1604. http://dx.doi.org/10.3390/plants9111604.
Повний текст джерелаАнотація:
Natural light intensities can rise several orders of magnitude over subsecond time spans, posing a major challenge for photosynthesis. Fluctuating light tolerance in the green alga Chlamydomonas reinhardtii requires alternative electron pathways, but the role of nonphotochemical quenching (NPQ) is not known. Here, fluctuating light (10 min actinic light followed by 10 min darkness) led to significant increase in NPQ/qE-related proteins, LHCSR1 and LHCSR3, relative to constant light of the same subsaturating or saturating intensity. Elevated levels of LHCSR1/3 increased the ability of cells to safely dissipate excess light energy to heat (i.e., qE-type NPQ) during dark to light transition, as measured with chlorophyll fluorescence. The low qE phenotype of the npq4 mutant, which is unable to produce LHCSR3, was abolished under fluctuating light, showing that LHCSR1 alone enables very high levels of qE. Photosystem (PS) levels were also affected by light treatments; constant light led to lower PsbA levels and Fv/Fm values, while fluctuating light led to lower PsaA and maximum P700+ levels, indicating that constant and fluctuating light induced PSII and PSI photoinhibition, respectively. Under fluctuating light, npq4 suffered more PSI photoinhibition and significantly slower growth rates than parental wild type, whereas npq1 and npq2 mutants affected in xanthophyll carotenoid compositions had identical growth under fluctuating and constant light. Overall, LHCSR3 rather than total qE capacity or zeaxanthin is shown to be important in C. reinhardtii in tolerating fluctuating light, potentially via preventing PSI photoinhibition.
4
Dinc, Emine, Lijin Tian, Laura M. Roy, Robyn Roth, Ursula Goodenough, and Roberta Croce. "LHCSR1 induces a fast and reversible pH-dependent fluorescence quenching in LHCII in Chlamydomonas reinhardtii cells." Proceedings of the National Academy of Sciences 113, no. 27 (June 22, 2016): 7673–78. http://dx.doi.org/10.1073/pnas.1605380113.
Повний текст джерелаАнотація:
To avoid photodamage, photosynthetic organisms are able to thermally dissipate the energy absorbed in excess in a process known as nonphotochemical quenching (NPQ). Although NPQ has been studied extensively, the major players and the mechanism of quenching remain debated. This is a result of the difficulty in extracting molecular information from in vivo experiments and the absence of a validation system for in vitro experiments. Here, we have created a minimal cell of the green alga Chlamydomonas reinhardtii that is able to undergo NPQ. We show that LHCII, the main light harvesting complex of algae, cannot switch to a quenched conformation in response to pH changes by itself. Instead, a small amount of the protein LHCSR1 (light-harvesting complex stress related 1) is able to induce a large, fast, and reversible pH-dependent quenching in an LHCII-containing membrane. These results strongly suggest that LHCSR1 acts as pH sensor and that it modulates the excited state lifetimes of a large array of LHCII, also explaining the NPQ observed in the LHCSR3-less mutant. The possible quenching mechanisms are discussed.
5
Gabilly, Stéphane T., Christopher R. Baker, Setsuko Wakao, Thien Crisanto, Katharine Guan, Ke Bi, Elodie Guiet, Carmela R. Guadagno, and Krishna K. Niyogi. "Regulation of photoprotection gene expression in Chlamydomonas by a putative E3 ubiquitin ligase complex and a homolog of CONSTANS." Proceedings of the National Academy of Sciences 116, no. 35 (August 12, 2019): 17556–62. http://dx.doi.org/10.1073/pnas.1821689116.
Повний текст джерелаАнотація:
Photosynthetic organisms use nonphotochemical quenching (NPQ) mechanisms to dissipate excess absorbed light energy and protect themselves from photooxidation. In the model green alga Chlamydomonas reinhardtii, the capacity for rapidly reversible NPQ (qE) is induced by high light, blue light, and UV light via increased expression of LHCSR and PSBS genes that are necessary for qE. Here, we used a forward genetics approach to identify SPA1 and CUL4, components of a putative green algal E3 ubiquitin ligase complex, as critical factors in a signaling pathway that controls light-regulated expression of the LHCSR and PSBS genes in C. reinhardtii. The spa1 and cul4 mutants accumulate increased levels of LHCSR1 and PSBS proteins in high light, and unlike the wild type, they express LHCSR1 and exhibit qE capacity even when grown in low light. The spa1-1 mutation resulted in constitutively high expression of LHCSR and PSBS RNAs in both low light and high light. The qE and gene expression phenotypes of spa1-1 are blocked by mutation of CrCO, a B-box Zn-finger transcription factor that is a homolog of CONSTANS, which controls flowering time in plants. CONSTANS-like cis-regulatory sequences were identified proximal to the qE genes, consistent with CrCO acting as a direct activator of qE gene expression. We conclude that SPA1 and CUL4 are components of a conserved E3 ubiquitin ligase that acts upstream of CrCO, whose regulatory function is wired differently in C. reinhardtii to control qE capacity via cis-regulatory CrCO-binding sites at key photoprotection genes.
6
Roach, Thomas, Chae Sun Na, Wolfgang Stöggl, and Anja Krieger-Liszkay. "The non-photochemical quenching protein LHCSR3 prevents oxygen-dependent photoinhibition in Chlamydomonas reinhardtii." Journal of Experimental Botany 71, no. 9 (January 16, 2020): 2650–60. http://dx.doi.org/10.1093/jxb/eraa022.
Повний текст джерелаАнотація:
Abstract Non-photochemical quenching (NPQ) helps dissipate surplus light energy, preventing formation of reactive oxygen species (ROS). In Chlamydomonas reinhardtii, the thylakoid membrane protein LHCSR3 is involved in pH-dependent (qE-type) NPQ, lacking in the npq4 mutant. Preventing PSII repair revealed that npq4 lost PSII activity faster than the wild type (WT) in elevated O2, while no difference between strains was observed in O2-depleted conditions. Low Fv/Fm values remained 1.5 h after moving cells out of high light, and this qH-type quenching was independent of LHCSR3 and not accompanied by losses of maximum PSII activity. Culturing cells in historic O2 atmospheres (30–35%) increased the qE of cells, due to increased LHCSR1 and PsbS levels, and LHCSR3 in the WT, showing that atmospheric O2 tensions regulate qE capacity. Colony growth of npq4 was severely restricted at elevated O2, and npq4 accumulated more reactive electrophile species (RES) than the WT, which could damage PSI. Levels of PsaA (PSI) were lower in npq4 grown at 35% O2, while PsbA (PSII) levels remained stable. We conclude that even at high O2 concentrations, the PSII repair cycle is sufficient to maintain net levels of PSII. However, LHCSR3 has an important function in protecting PSI against O2-mediated damage, such as via RES.
7
Kondo, Toru, Jesse B. Gordon, Alberta Pinnola, Luca Dall’Osto, Roberto Bassi, and Gabriela S. Schlau-Cohen. "Microsecond and millisecond dynamics in the photosynthetic protein LHCSR1 observed by single-molecule correlation spectroscopy." Proceedings of the National Academy of Sciences 116, no. 23 (May 17, 2019): 11247–52. http://dx.doi.org/10.1073/pnas.1821207116.
Повний текст джерелаАнотація:
Biological systems are subjected to continuous environmental fluctuations, and therefore, flexibility in the structure and function of their protein building blocks is essential for survival. Protein dynamics are often local conformational changes, which allows multiple dynamical processes to occur simultaneously and rapidly in individual proteins. Experiments often average over these dynamics and their multiplicity, preventing identification of the molecular origin and impact on biological function. Green plants survive under high light by quenching excess energy, and Light-Harvesting Complex Stress Related 1 (LHCSR1) is the protein responsible for quenching in moss. Here, we expand an analysis of the correlation function of the fluorescence lifetime by improving the estimation of the lifetime states and by developing a multicomponent model correlation function, and we apply this analysis at the single-molecule level. Through these advances, we resolve previously hidden rapid dynamics, including multiple parallel processes. By applying this technique to LHCSR1, we identify and quantitate parallel dynamics on hundreds of microseconds and tens of milliseconds timescales, likely at two quenching sites within the protein. These sites are individually controlled in response to fluctuations in sunlight, which provides robust regulation of the light-harvesting machinery. Considering our results in combination with previous structural, spectroscopic, and computational data, we propose specific pigments that serve as the quenching sites. These findings, therefore, provide a mechanistic basis for quenching, illustrating the ability of this method to uncover protein function.
8
Tian, Lijin, Wojciech J. Nawrocki, Xin Liu, Iryna Polukhina, Ivo H. M. van Stokkum, and Roberta Croce. "pH dependence, kinetics and light-harvesting regulation of nonphotochemical quenching inChlamydomonas." Proceedings of the National Academy of Sciences 116, no. 17 (April 8, 2019): 8320–25. http://dx.doi.org/10.1073/pnas.1817796116.
Повний текст джерелаАнотація:
Sunlight drives photosynthesis but can also cause photodamage. To protect themselves, photosynthetic organisms dissipate the excess absorbed energy as heat, in a process known as nonphotochemical quenching (NPQ). In green algae, diatoms, and mosses, NPQ depends on the light-harvesting complex stress-related (LHCSR) proteins. Here we investigated NPQ inChlamydomonas reinhardtiiusing an approach that maintains the cells in a stable quenched state. We show that in the presence of LHCSR3, all of the photosystem (PS) II complexes are quenched and the LHCs are the site of quenching, which occurs at a rate of ∼150 ps−1and is not induced by LHCII aggregation. The effective light-harvesting capacity of PSII decreases upon NPQ, and the NPQ rate is independent of the redox state of the reaction center. Finally, we could measure the pH dependence of NPQ, showing that the luminal pH is always above 5.5 in vivo and highlighting the role of LHCSR3 as an ultrasensitive pH sensor.
9
Dikaios, Ioannis, Christo Schiphorst, Luca Dall’Osto, Alessandro Alboresi, Roberto Bassi, and Alberta Pinnola. "Functional analysis of LHCSR1, a protein catalyzing NPQ in mosses, by heterologous expression in Arabidopsis thaliana." Photosynthesis Research 142, no. 3 (July 3, 2019): 249–64. http://dx.doi.org/10.1007/s11120-019-00656-3.
Повний текст джерела
10
Pinnola, Alberta, Hristina Staleva-Musto, Stefano Capaldi, Matteo Ballottari, Roberto Bassi, and Tomáš Polívka. "Electron transfer between carotenoid and chlorophyll contributes to quenching in the LHCSR1 protein from Physcomitrella patens." Biochimica et Biophysica Acta (BBA) - Bioenergetics 1857, no. 12 (December 2016): 1870–78. http://dx.doi.org/10.1016/j.bbabio.2016.09.001.
Повний текст джерелаДисертації з теми "LHCSR1"
1
Pietrzykowska, Malgorzata. "The roles of Lhcb1 och Lhcb2 in regulation of photosynthetic light harvesting." Doctoral thesis, Umeå universitet, Institutionen för fysiologisk botanik, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-97987.
Повний текст джерелаАнотація:
Photosynthesis in higher plants relies upon collection of light by chlorophyll molecules associated with light harvesting chlorophyll a/b-binding (LHC) proteins. The two most abundant of these are Lhcb1 and Lhcb2, which make up light harvesting complex (LHC) II trimers. They are also involved in facilitating state transitions, a process during which energy balancing between photosystem (PS) II and I is achieved. Overexcitation of PSII reduces the plastoquinone pool which activates STN7, a kinase, that phosphorylates a threonine residue on Lhcb1 and Lhcb2. In order to studythe kinetics of this we developed antibodies capable of recognizingphosphorylated forms of each of these proteins. This showed that Lhcb2 is more rapidly phosphorylated than Lhcb1, that there are no differences in the migration of phosphorylated and non-phosphorylated forms of Lhcb1 and Lhcb2 and that the majority of phosphorylated LHCII (P-Lhcb1 and PLhcb2) are associated with super- and megacomplexes. Furthermore, a state 2-specific LHCII-PSI-LHCI band contains P-Lhcb2 but almost no P-Lhcb1, and a band corresponding to M trimers (band 4 from sucrose gradients, composed of LHCII, CP24 and CP29), contains only P-Lhcb1 but no P-Lhcb2. We also developed artificial microRNA lines specifically depleted in either Lhcb1 or Lhcb2, amiLhcb1 and amiLhcb2 respectively. We show that the roles of Lhcb1 and Lhcb2 in state transitions are complementary. Lhcb1 modulate the size of grana stacks. In the absence of Lhcb1 only a few LHC trimers are formed, while in the absence of Lhcb2, the antenna looks like in the wild type although the plants cannot perform state transitions normally. Trimers containing P-Lhcb2 functionally detach from PSII and connect to PSI to balance the relative excitation pressure. State transitions only occur when both Lhcb1 and Lhcb2 are present, presumably in a (Lhcb1)2 Lhcb2 heterotrimer. In absence of Lhcb2, the LHCII-PSI-LHCI supercomplex is not formed indicting that P-Lhcb2 mediates attachment of LHCII to PSI. We tried complementing amiLhcb2 with modified Lhcb2 genes coding for proteins with altered amino acids, Arg2 to Lys or the phosphorylatable Thr3 residue to Asn or Ser. Introduction of the additional gene often causes loss of amiRNA-inhibition, however we could confirm that substitution of the Thr3 with Asn led to the absence of Lhcb2 phosphorylation and thus no state transition.Klorofyll a/b-bindande proteiner (s k light harvesting chlorophyll a/b-binding proteins eller LHC proteiner) är viktiga för högre växters fotosyntes, då deras klorofyllmolekyler skördar solljuset. Två av dessa proteiner, Lhcb1 och Lhcb2, bygger upp ”LHCII trimerer” och finns i större mängd än de andra och dessa är även viktiga för s k ”state transtions”, en process som ser till att fotosystem (PS) I och PSII exciteras lika mycket. Om PSII exciteras för mycket reduceras plastoquinon-poolen som i sin tur aktiverar ett proteinkinas, STN7, som fosforylerar en av Lhcb1/Lhcb2s treoniner. För att studera denna fosforylering har vi utvecklat antikroppar som är specifika för dessa fosforylerade former av proteinerna, och vi använde dem för att visa att Lhcb2 fosforyleras snabbare än Lhcb1, och att största delen av det fosforylerade proteinerna (P-Lhcb1 och P-Lhcb2) finns i s k super- eller megakomplex. Ett komplex som bara finns finns i ”state 2” består av LHCII, PSI och LHCI, och det innehåller endast P-Lhcb2 men nästan inget P-Lhcb1, och ett band som består av LHCII, CP24 och CP29 innehåller endast PLhcb1. Vi skapade artificiella mikro-RNA-linjer, amiLhcb1 och amiLhcb2, som saknade antingen Lhcb1 eller Lhcb2. Lhcb1 påverkar höjden av grana stackarna. Med hjälp av dessa visade vi att Lhcb1 och Lhcb2 har komplementära roller för state transitions, saknas Lhcb1 gör växten bara få LHCII trimerer, medan om Lhcb2 gör växten antennener som liknar vildtypens, men den kan inte utföra state transitions som den. Mängden Lhcb1 påverkar storleken av ”grana stacks”. Trimerer som innehåller PLhcb2 kopplas över från PSII till PSI för att balansera excitationstrycket. Både Lhcb1 och Lhcb2, antagligen i trimerer bestående av en Lhcb2 och the Lhcb1, behövs för state transitions. Saknas Lhcb2 bildas inga komplex bestående av LHCII, PSI och LHCI, vilket visar att P-Lhcb2 antagligen möjliggör LHCIIs bindning till PSI. Vi försökte komplementera amiLhcb2 med Lhcb2 gener där amino syror bytts ut, Arg2 till Lys eller den fosforylerbara Thr3 till Asn eller Ser. När denna gen introducerades försvann dock ofta amiRNA-inhiberingen, men vi kunde visa att om Thr3 ersattes med Asn skedde inga state transitions.
2
PARADISO, ELIA. "AZIONE DEI LISOSFINGOLIPIDI E DELLE GONADOTROPINE COME DETERMINANTI DELLA REGOLAZIONE ENDOCRINA DEL FOLLICOLO OVARICO." Doctoral thesis, Università degli studi di Modena e Reggio Emilia, 2022. http://hdl.handle.net/11380/1278599.
Повний текст джерелаАнотація:
La sfingosina-1 fosfato (S1P) è un lisosfingolipide presente nel liquido follicolare ovarico insieme alle gonadotropine glicoproteiche. L'ormone luteinizzante (LH) e l'ormone follicolo-stimolante (FSH) sono necessari per garantire la steroidogenesi, la gametogenesi e la riproduzione. La gonadotropina corionica umana (hCG) agisce durante la gravidanza sullo stesso recettore di LH, LHCGR, per stimolare la produzione di progesterone da parte del corpo luteo e mantenere la gravidanza. Inoltre, le gonadotropine sono fattori di crescita e differenziazione, che modulano la proliferazione cellulare, la sopravvivenza e l'apoptosi. Sia S1P che le gonadotropine esercitano le loro funzioni fisiologiche legandosi a recettori accoppiati a proteine G (GPCR). S1P si lega e attiva cinque recettori specifici, S1P1-5, modulando diverse vie di segnalazione. S1P1 e S1P3 sono altamente espressi nelle cellule primarie della granulosa luteina umana (hGLC).
Questo studio mira a caratterizzare il ruolo della segnalazione intracellulare indotto da S1P e gonadotropine nel determinare lo sviluppo del follicolo ovarico in vitro. A questo scopo sono state utilizzate granulose umane e linee cellulari che esprimono stabilmente FSHR e LHCGR sotto il controllo di un promotore inducibile. Sono state valutate l’eterodimerizzazione di S1PR1 con LHCGR/FSHR e GPER e la cinetica delle proteine G e il reclutamento della β-arrestina 2 con LHCGR mediate da LH e hCG, così come l'attivazione di secondi messaggeri e l’internalizzazione di LHCGR in vitro.
hGLC e hGL5 sono state trattate con dose fissa (0,1 μM) di S1P e con specifici agonisti di S1P1 e S1P3, SEW2871 e CYM5541. Nelle cellule della granulosa, S1P e, in maniera minore, SEW2871 e CYM5541, hanno indotto pCREB. Non è stata rilevata alcuna produzione di cAMP e l'attivazione di pCREB è avvenuta anche in presenza dell'inibitore della PKA H-89. Inoltre, pCREB S1P-dipendente è stata attenuata dall'inibitore di MEK U0126 e da un bloccante dei canali Ca2+ di tipo L, il verapamil. La completa inibizione di pCREB si è verificata bloccando S1P2 o S1P3 con specifici antagonisti. pCREB S1P-dipendente ha indotto l’espressione di FOXO1 ed EREG, confermando il ruolo esclusivo delle gonadotropine e delle interleuchine in questo processo, ma non ha influenzato la steroidogenesi.
hCG induce l'accoppiamento Gαs-, Gq e β-arrestin 2 con LHCGR in modo più efficace rispetto a LH. In presenza di Dynasore, un inibitore dell'internalizzazione, hCG mantiene una cinetica simile, ma non LH, che necessita dell'endocitosi di LHCGR per indurre l'accoppiamento del recettore. Questi dati riflettono la cinetica ormone-specifica dell'attivazione dell'effettore a valle correlata alle proteine G e alla β -arrestina 2. LH ha indotto un rapido aumento di cAMP ed è più potente di hCG nell'attivazione di pERK1/2. È interessante notare che la cinetica dell'aumento di Ca2+ intracellulare indotto da hCG dipende dall'internalizzazione di LHCGR rispetto a LH che non riesce a indurre un aumento di Ca2+ intracellulare. È stata valutata l'interazione tra LHCGR e specifici marcatori degli endosomi per studiare l'internalizzazione di LHCGR mediata dalle gonadotropine. LH è più potente di hCG nel promuovere il riciclaggio di LHCGR.
Questo studio ha dimostrato che S1P può indurre un'attivazione di pCREB indipendente da cAMP nelle cellule della granulosa, sebbene ciò non sia sufficiente per indurre la sintesi del progesterone. L'espressione genica di FOXO1 ed EREG indotta da S1P suggerisce che l'attivazione dell'asse S1P-S1PR può cooperare con le gonadotropine nel modulare lo sviluppo del follicolo. L'internalizzazione di LHCGR è fondamentale per modulare i segnali specifici di LH e hCG che influenzano le proteine G e l'accoppiamento β -arrestina 2 e le cascate di segnalazione a valle.Sphingosine-1 phosphate (S1P) is a lysosphingolipid present in the ovarian follicular fluid together with glycoprotein hormone gonadotropins. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are necessary to ensure steroidogenesis, gametogenesis and reproduction. Human chorionic gonadotropin (hCG) acts during pregnancy via the same receptor for LH, the LHCGR, to stimulate progesterone production by the corpus luteum and maintaining pregnancy. In addition, gonadotropins are growth and differentiation factors, modulating cell proliferation, survival and apoptosis. Both S1P and gonadotropins exert their physiological functions by binding cognate G protein-coupled receptors (GPCRs). At nanomolar concentrations, S1P binds and activates five specific receptors, known as S1P1-5, modulating different signaling pathways. S1P1 and S1P3 are highly expressed in human primary granulosa lutein cells (hGLC). This study aims to characterize the role of S1P- and gonadotropins-induced signaling in determining ovarian follicle development in vitro. To this purpose were used human granulosa, cell lines stably expressing FSHR and LHCGR under the control of an inducible promoter, treated with gonadotropins and S1P. S1PR1 heterodimerization to LHCGR/FSHR and GPER and the kinetics of LH- and hCG-mediated G proteins and β-arrestin 2 coupling to LHCGR were evaluated, such as the activation of related second messengers and kinases, and the role of gonadotropins-induced LHCGR internalization in vitro. hGLC and hGL5 cells were treated with a fixed dose (0.1 μM) of S1P, or by S1P1- and S1P3-specific agonists SEW2871 and CYM5541. In granulosa cells, S1P and, at a lesser extent, SEW2871 and CYM5541, potently induced pCREB. No cAMP production was detected and pCREB activation occurred even in the presence of the PKA inhibitor H-89. Moreover, S1P-dependent pCREB was dampened by MEK inhibitor U0126 and by the L-type Ca2+ channel blocker verapamil. The complete inhibition of pCREB occurred by blocking either S1P2 or S1P3 with the specific receptor antagonists, or under PLC/PI3K depletion. S1P-dependent pCREB induced FOXO1 and EREG, confirming the exclusive role of gonadotropins and interleukins in this process, but did not affect steroidogenesis. The kinetics of LH and hCG-mediated G proteins and β-arrestin 2 coupling to their receptor, and the activation of related second messengers and kinases were evaluated by BRET. hCG induces Gαs-, Gq and β-arrestin 2 coupling to LHCGR more effectively than LH. Under receptor internalization blockade by Dynasore, hCG maintains similar kinetics, but not LH, which needs LHCGR endocytosis for inducing receptor coupling. These data reflect hormone-specific kinetics of downstream effector activation related to G proteins and β-arrestin 2. LH induced a rapid cAMP increase and is more potent than hCG in activating pERK1/2. Interestingly, the kinetic of hCG-induced intracellular Ca2+ increase depends on LHCGR internalization than LH that fails in inducing intracellular Ca2+ increase, consistently with weak Gq recruitment. The interaction between LHCGR and specific markers of endosomes were evaluated to estimate LHCGR internalization mediated by gonadotropins. Indeed, LH is more potent than hCG in promoting LHCGR recycling. This study demonstrated that S1P may induce a cAMP-independent activation of pCREB in granulosa cells, although this is not sufficient to induce progesterone synthesis. S1P-induced FOXO1 and EREG gene expression suggests that the activation of S1P-S1PR axis may cooperate with gonadotropins in modulating follicle development. LHCGR internalization is fundamental for modulating LH- and hCG-specific signals impacting G proteins and β-arrestin 2 coupling, and the downstream signaling cascades.
3
Bäck, Siri. "No Lhcb1 or Lhcb2 isoforms alone has a significant effect on state transitions." Thesis, Umeå universitet, Institutionen för fysiologisk botanik, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-65435.
Повний текст джерела
4
Chaves, Marina Platzeck. "EXPRESSÃO DIFERENCIAL DO RECEPTOR DE LH, DA PROTEÍNA DE LIGAÇÃO DE MRNA DO LHR, BTA-MIR-222 E ENZIMAS ESTEROIDOGÊNICAS NO OVÁRIO BOVINO EM DESENVOLVIMENTO." Universidade do Oeste Paulista, 2018. http://bdtd.unoeste.br:8080/jspui/handle/jspui/1117.
Повний текст джерелаАнотація:
Submitted by Michele Mologni (mologni@unoeste.br) on 2018-11-30T12:45:47Z
No. of bitstreams: 1
Marina Platzeck Chaves.pdf: 891914 bytes, checksum: 43d527b64ad46e92f25496042406c5e9 (MD5)Made available in DSpace on 2018-11-30T12:45:47Z (GMT). No. of bitstreams: 1 Marina Platzeck Chaves.pdf: 891914 bytes, checksum: 43d527b64ad46e92f25496042406c5e9 (MD5) Previous issue date: 2018-05-30
Steroids and gonadotrophins are essential for the regulation of antral follicular development and the late stages of preantral development. Although the luteinizing hormone receptor (LHR) has been detected in the preantral follicles of rats, rabbits, and pigs, the expression of this receptor in bovine fetal ovary has not been demonstrated. The present study aimed to quantify the expression of the LHR and the mRNA abundance of the genes LHR binding protein (LRBP), STAR, HSD3B1, CYP17A1, and CYP19A1 during the development of bovine fetal ovary. In addition, we aimed to identify and quantify the expression of bta-miR-222 (a regulatory microRNA of the LHCGR gene). In summary, LHR expression was observed in the preantral follicle in bovine fetal ovary, from oogonias to primordial, primary and secondary stages, and the mRNA abundance was lower on day 150 than day 60. However, the mRNA abundance of LRBP followed the opposite pattern. The LHR protein was detected in oogonia, primordial, primary, and secondary follicles. Moreover, both oocytes and granulosa cells showed positive immunostaining for LHR. Similar to LRBP, the abundance of bta-miR-222 was higher on day 150 than day 60 or 90 of gestation. With regard to the gene expression of steroidogenic enzymes; only the mRNA abundance of STAR was higher on day 150 than on day 60. In conclusion, these results suggested the involvement of LHCGR/LRBP regulation with mechanisms related to the development of preantral follicles, especially during the establishment of secondary follicles. Furthermore, the present data reinforced that the reduced expression of LHR mRNA in bovine fetal ovaries on day 150 was related to the higher expression of LRBP and bta-miR-222.
Esteroides e gonadotrofinas são essenciais para a regulação do desenvolvimento folicular antral e os estágios finais do desenvolvimento pré-antral. Embora o receptor do hormônio luteinizante (LHR) tenha sido detectado nos folículos pré-antrais de ratos, coelhos e porcos, a expressão deste receptor no ovário fetal bovino não foi demonstrada. O presente estudo teve como objetivo quantificar a expressão do LHR e a abundância de mRNA da proteína de ligação LHR (LRBP), STAR, HSD3B1, CYP17A1 e CYP19A1 durante o desenvolvimento do ovário fetal bovino. Além disso, objetivamos identificar e quantificar a expressão de bta-miR-222 (microRNA regulador do gene LHCGR). Em resumo, a expressão de LHR foi observada no folículo pré-antral no ovário fetal de bovino e a abundância de mRNA foi menor no dia 150 do que no dia 60. No entanto, a abundância de mRNA da LRBP seguiu o padrão oposto. Semelhante a LRBP, a abundância de bta-miR-222 foi maior no dia 150 do que no dia 60 ou 90. Com relação à expressão gênica de enzimas esteroidogênicas; apenas a abundância de mRNA de STAR foi maior no dia 150 do que no dia 60. A proteína LHR foi detectada em oogônia, folículos primordiais, primários e secundários. Além disso, ambos os oócitos e células da granulosa apresentaram imunolocalização positiva para LHR. Em conclusão, estes resultados sugeriram o envolvimento da regulação do LHCGR / LBPB com mecanismos relacionados ao desenvolvimento de folículos pré-antrais, especialmente durante o estabelecimento de folículos secundários. Além disso, os presentes dados reforçaram que a expressão reduzida de mRNA de LHR em ovários fetais bovinos no dia 150 estava relacionada à maior expressão de LRBP e bta-miR-222.
5
LAZZARETTI, CLARA. "Azione Molecolare E Cellulare Degli Ormoni Della Riproduzione." Doctoral thesis, Università degli studi di Modena e Reggio Emilia, 2022. http://hdl.handle.net/11380/1278344.
Повний текст джерелаАнотація:
Classicamente, la segnalazione dipendente dall’attivazione del cAMP mediata dal recettore dell'ormone follicolo-stimolante (FSHR) e dal recettore dell'ormone luteinizzante (LH) (LHCGR) favorisce la crescita del follicolo ovarico umano e la maturazione degli ovociti. Tuttavia, esistono dati in vitro contraddittori che suggeriscono un diverso significato fisiologico della segnalazione di cAMP mediata da FSHR, mostrando allo stesso tempo l'attivazione di eventi steroidogenici e pro-apoptotici. Questi segnali possono essere alterati dagli estrogeni che inducono eventi anti-apoptotici attraverso i loro recettori nucleari e all'azione non genomica di un recettore degli estrogeni accoppiato a proteine G (GPER). Lo scopo del progetto è chiarire il ruolo degli estrogeni/gonadotropine e dei loro recettori di membrana nella regolazione della fisiologia ovarica e nella selezione del follicolo dominante. In questo studio è stato dimostrato che GPER forma dimeri sia con FSHR che con LHCGR sulla superficie cellulare di cellule HEK293 che sovraesprimono i due recettori e di cellule primarie della granulosa luteina umana (hGLC). Gli eteromeri FSHR/GPER riprogrammano i segnali del cAMP e di morte, in stimoli proliferativi fondamentali per sostenere la sopravvivenza degli ovociti. Nelle cellule della granulosa umana, i segnali di sopravvivenza mancano quando è presente un rapporto FSHR:GPER elevato, che influisce negativamente sulla maturazione del follicolo e si correla con l'accoppiamento preferenziale alla proteina Gαs, l’attivazione della via cAMP/PKA e la capacità di risposta ad FSH dei pazienti sottoposti a stimolazione ovarica controllata. Gli eteromeri FSHR/GPER, invece, mediano segnali anti-apoptotici e proliferativi dipendenti da FSH tramite il dimero Gβγ e la compromissione della formazione degli eteromeri o il knockdown GPER aumenta la morte cellulare e la steroidogenesi FSH-dipendenti. Al contrario, il complesso GPER/LHCGR non influenza la produzione di cAMP indotta da LH e hCG e non compromette l'attivazione della via cAMP/PKA. Ciò si evince dalla simile fosforilazione di CREB ed ERK1/2 e dalla stessa produzione di progesterone in hGLC trattate con siRNA contro GPER e quelle trattato con mock. È interessante notare che GPER riduce l’accoppiamento LHCGR/Gαq e di conseguenza impedisce il rilascio intracellulare di Ca2+ e l'accumulo di IP1, dopo stimolazione con LH e hCG, in cellule HEK293 che co-esprimono LHCGR e GPER rispetto alle cellule che esprimono solo LHCGR. Inoltre, è stato dimostrato che in presenza di GPER la cinetica dell'internalizzazione di FSHR attraverso endosomi precoci e tardivi è ridotta, suggerendo la sua capacità di bloccare FSHR a livello intracellulare e riducendo il riciclaggio di FSHR sulla membrana. Infatti, l'internalizzazione di FSHR è necessaria affinché GPER inibisca la risposta del cAMP indotta da FSH. Secondo i nostri risultati, gli estrogeni sono selettivamente coinvolti nella regolazione dei segnali pro e anti-apoptotici, nell'internalizzazione dei recettori attraverso i complessi FSHR/GPER e nella modulazione della cascata di segnali mediata da LHCGR. I nostri risultati indicano come la maturazione degli ovociti dipenda dalla capacità del GPER di modulare i segnali selettivi di FSHR e LHCGR, indicando che gli eteromeri dei recettori delle gonadotropine possono essere un marker della proliferazione cellulare.Classically, follicle-stimulating hormone receptor (FSHR) and luteinizing hormone (LH) receptor (LHCGR) -driven cAMP-mediated signaling boosts human ovarian follicle growth and oocyte maturation. However, contradicting in vitro data suggest a different view on physiological significance of FSHR-mediated cAMP signalling, showing at the same time the activation of steroidogenic and pro-apoptotic events. These signals can be impaired by estrogens inducing anti-apoptotic events via nuclear receptors and non-genomic action of a G protein-coupled estrogen receptor (GPER). The aim of the project is to better understand the role of estrogens/gonadotropins and their membrane receptors in regulating ovarian physiology and the selection of the dominant follicle. In this study it was demonstrated that GPER heteromerizes both with FSHR and LHCGR at the cell surface of HEK293 cells overexpressing the two receptors as well as human primary granulosa lutein cells (hGLC). FSHR/GPER heteromers reprogram cAMP/death signals into proliferative stimuli fundamental for sustaining oocyte survival. In human granulosa cells, survival signals are missing at high FSHR:GPER ratio, which negatively impacts follicle maturation and strongly correlates with preferential Gαs protein/cAMP-pathway coupling and FSH responsiveness of patients undergoing controlled ovarian stimulation. In contrast, FSHR/GPER heteromers triggered anti-apoptotic/proliferative FSH signaling delivered via the Gβγ dimer, whereas impairment of heteromer formation or GPER knockdown enhanced the FSH-dependent cell death and steroidogenesis. On the other hand, GPER/LHCGR complex does not affect the LH and hCG-induced cAMP production and do not compromise the activation of the cAMP/PKA pathway, as it is indicated by similar CREB and ERK1/2 phosphorylation and same progesterone production in hGLC treated with siRNA against GPER, and the mock-treated one. Interestingly, GPER displace the LHCGR/Gαq coupling and consequently impedes the intracellular Ca2+ release and IP1 accumulation in LHCGR-GPER co-expressing HEK293 cells upon LH and hCG treatment compared to LHCGR-expressing cells. Also, it was demonstrated that in presence of GPER the kinetic of FSHR internalization through early and late endosomes is reduced, suggesting its ability to blockade FSHR at the intracellular level and reduce FSHR recycling on cell membrane. Indeed, FSHR internalization is necessary for GPER to inhibit FSH-induced cAMP response. According to our results, estrogens are selectively involved in the regulation of pro- and anti-apoptotic signals and receptor internalization through FSHR/GPER complexes and in modulation of LHCGR-mediated signaling cascade. Our findings indicate how oocyte maturation depends on the capability of GPER to shape FSHR and LHCGR selective signals, indicating hormone receptor heteromers may be a marker of cell proliferation.
6
Santos, Priscila Helena dos. "Impactos da superestimulação ovariana sobre a diferenciação das células da granulosa bovina." Botucatu, 2017. http://hdl.handle.net/11449/150618.
Повний текст джерелаАнотація:
Orientador: Anthony César de Souza CastilhoResumo: A superestimulação ovariana é uma biotecnologia amplamente empregada na espécie bovina para a obtenção de múltiplas ovulações. Com este objetivo diversos protocolos superestimulatórios surgiram, dentre eles o protocolo P-36 e sua variação, o protocolo P-36/eCG. Ambos os tratamentos utilizam o hormônio folículo estimulante (FSH) na indução do crescimento folicular. Como é acreditado que no último dia do tratamento, as células da granulosa folicular possuam receptores do hormônio luteinizante (LH; LHR), duas últimas doses de FSH foram substituídas pela administração de gonadotrifina coriónica equina (eCG; P-36/eCG). A molécula de eCG possui atividade tanto LH quanto FSH por se ligar a ambos receptores, aumentando a resposta ovulatória. Os dois tratamentos têm demonstrado eficácia quanto ao desenvolvimento de oócitos competentes para a produção embrionária, no entanto pouco se sabe sobre seus efeitos na diferenciação celular no folículo ovariano. Por isso, o presente estudo investigou os efeitos da superestimulação ovariana com FSH (P-36) ou FSH combinado com eCG (P-36/eCG) sobre aspectos bioquímicos e a produção de hormônios esteroides. Adicionalmente, quantificou-se a abundância de miRNAs reguladores da expressão do mRNA do LHR e outros miRNAs relacionados com o desenvolvimento folicular ovariano. Os resultados obtidos mostram que os tratamentos superestimulatórios alteram o perfil bioquímico intrafolicular e a concentração de estradiol no plasma. Aliado a isso, também alteram... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Ovarian overstimulation is a biotechnology widely used in the bovine species to obtain multiple ovulations. With this objective, several protocols were introduced, including the P-36 protocol and its variation, the P-36/eCG protocol. Both treatments use follicle stimulating hormone (FSH) to induce the follicular growth. As it is believed that on the last day of treatment, follicular granulosa cells have luteinizing hormone (LHR) receptors, two last doses of FSH have been replaced by administration of equine chorionic gonadotrifine (eCG; P-36/eCG). The eCG molecule has LH and FSH activity by binding to both receptors, increasing the ovulatory response. Both treatments has demonstrated efficacy in the development of oocytes competent for embryo production, however little is known about their effects on cell differentiation in the ovarian follicle. Therefore, the present study investigated the effects of ovarian superstimulation using FSH (P-36) or FSH combined with eCG (P-36/eCG) on biochemical aspects and production of steroid hormones. In addition, the abundance of miRNAs regulating the expression of LHR mRNA and other miRNAs related to ovarian follicular development. Results demonstrated that superstimulatory treatments alter the intrafollicular biochemical profile and the plasma estradiol concentration. In addition, they also alter the expression of LHR and miRNAs regulating LHR mRNA expression, possibly modulating ovulatory capacity in superstimulated ovarian follicles.
Mestre
7
Kulkarni, Rewa M. "CO-LOCALIZATION OF POLYCYSTIC OVARY SYNDROME CANDIDATE GENE PRODUCTS IN HUMAN THECA CELLS SUGGESTS NOVEL SIGNALING PATHWAYS." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5741.
Повний текст джерелаАнотація:
Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility and the most common endocrinopathy of women of reproductive age. Genome-wide association studies (GWAS) identified a number of loci associated PCOS in different ethnic populations, including women with Asian and European ancestry. Replication studies have confirmed some of these associations. Among the loci identified are those located near the LH receptor gene (LHCGR), a clathrin-binding protein gene (DENND1A) that also functions as a guanine nucleotide exchange factor, and the gene encoding RAB5B, a GTPase and protein involved in vesicular trafficking. The functional significance of one of these GWAS candidates (DENND1A) was supported by our discovery that a truncated protein splice variant of DENND1A termed DENND1A.V2, is elevated in PCOS theca cells, and that forced expression of DENND1A.V2 in normal theca cells increased CYP11A1 and CYP17A1 expression and androgen synthesis, a hallmark of PCOS. We previously proposed that the PCOS GWAS loci could be assembled into a functional network that contributes to altered gene expression in ovarian theca cells, resulting in increased androgen synthesis. Here we demonstrate the localization of LHCGR, DENND1AV.2 and RAB5B proteins in various cellular compartments in normal and PCOS theca cells. hCG and forskolin stimulation affects the distribution and co-localization of DENND1A.V2 and RAB5B in various cellular compartments This cytological evidence supports our PCOS gene network concept, and raises the intriguing possibility that LHCGR activation, via a cAMP-mediated process, promotes the translocation of DENND1A.V2 and RAB5B-containing vesicles from the PCOS theca cell cytoplasm into the nucleus, resulting in increased transcription of genes involved in androgen synthesis.
8
Böckenfeld, Yvonne [Verfasser], and Michael [Akademischer Betreuer] Zitzmann. "Polymorphismen des neuentdeckten Exons 6a auf dem LHCGR-Gen und ihre Assoziation zum Maldescensus testis / Yvonne Böckenfeld. Betreuer: Michael Zitzmann." Münster : Universitäts- und Landesbibliothek der Westfälischen Wilhelms-Universität, 2012. http://d-nb.info/1027021212/34.
Повний текст джерела
9
Schulze, Claudia. "Vergleichende immunhistochemische Untersuchungen zum LH/hCG-Rezeptor (LHCGR) im Urothel und Detrusor der Harnblase mit Veränderungen bei Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC)." Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-148042.
Повний текст джерелаАнотація:
BPS/IC (Bladder Pain Syndrome/Interstitial Cystitis) ist ein sehr schweres und noch weitgehend unverstandenes Krankheitsbild in der Urologie. Viele Frauen sind im Alltag durch den ständigen Harndrang und die Schmerzen stark eingeschränkt und von Depressionen betroffen. Die Aufklärung der Pathogenese ist deshalb sehr wichtig, um eine adäquate Therapie für die Betroffenen zu entwickeln und die Krankheit möglichst frühzeitig diagnostizieren zu können. Das Schwangerschaftshormon hCG (humanes Choriongonadotropin) besitzt differenzierende und wachstumsfördernde Eigenschaften und eine Rolle in der Urothelregeneration und – stabilisierung scheint möglich. Daher ist das Ziel dieser Arbeit seinen Rezeptor, den LHCGR (Luteinizing-Hormone/Choriogonadotropin Rezeptor), in der Harnblase nachzuweisen und die urothelialen und muskulären Charakteristika zwischen gesunden und an BPS/IC erkrankten Harnblasen zu vergleichen. Die Darstellung des LHCGR erfolgte auf Proteinebene mittels indirekter Immunfluoreszenz und auf mRNA-Ebene durch Standard-PCR. Es zeigten sich im Urothel von Harnblase und Ureter 5 unterschiedliche Verteilungsmuster des Rezeptors hinsichtlich seiner Expression in verschiedenen Zellschichten und seiner subzellulären Lokalisation. Je nach Urothelzustand und zwischen den Entitäten Kontroll- bzw. BPS/IC-Harnblase variierten diese Muster in ihrer Häufigkeit. In anderen Epithelien, wie dem Vaginalepithel, änderte sich die zelluläre Verteilung des LHCGR in Abhängigkeit vom Differenzierungsgrad der Zellen. Es scheint möglich, dass auch die Rezeptorexpression in Urothelzellen deren verschiedene Differenzierungszustände widerspiegelt. Dies unterstützt den für hCG vermuteten Einfluss auf die Epithelregeneration. Ein Vergleich der urothelialen Fluoreszenzintensitäten zwischen weiblichen Kontroll – und BPS/IC-Harnblasen zeigte eine signifikant stärkere Expression des Rezeptors bei erkrankten Patienten. Dem gegenüber war kein Unterschied im Detrusor, weder zwischen Kontroll – und BPS/IC-Harnblasen noch im geschlechtsspezifischen Vergleich, festzustellen. Damit scheint der Rezeptor seine Hauptaufgabe vorrangig im Urothel zu entfalten. Die Korrelationsanalysen ergaben keinen signifikanten Zusammenhang zwischen dem Erkrankungsalter (Zeitpunkt der Diagnosestellung und Biopsieentnahme) und der LHCGR-Immunfluoreszenz. Ein endokrinologischer Einfluss auf die Rezeptorexpression wurde dadurch unwahrscheinlich und unterstützt die immer akzeptiertere Auffassung, dass BPS/IC nicht mehr mit der Menopause assoziiert ist. Neben dem Urothel und Detrusor zeigten auch Lamina propria und Gefäße von Harnblase und Ureter die Expression des LHCGR in der Immunhistochemie. Unterschiedliche Clustermuster des Rezeptors im Detrusor ließen auf die Oligomerisierung des Rezeptors schließen. Die Bedeutung dieser Zusammenschlüsse ist jedoch noch unklar, wobei unterschiedliche funktionelle Zustände des Rezeptors vermutet werden. Orientierung bieten andere Rezeptoren, die durch Dimerisierung verschiedener Rezeptorvarianten ihre Funktionalität verbessern oder verschlechtern konnten. Obwohl für keine bisher entdeckte Variante des LHCGR eine definitive Aufgabe ermittelt werden konnte, scheinen doch viele Varianten auch unterschiedliche Funktionen wahrnehmen zu können. Besonders auf der Regulierbarkeit des Rezeptors mittels interagierender Splicevarianten sollte das Augenmerk zukünftiger Studien liegen. Ob durch Komplexbildung verschiedener Varianten oder Bildung nichtfunktioneller trunkierter Rezeptoren, die Kontrollmöglichkeiten sind vielfältig und können auch auf Liganden wirken. Letztlich ließ der Nachweis des LHCGR in allen Schichten von Harnblase und Ureter eher eine globale Rolle des Rezeptors im Harntrakt des Menschen vermuten. Dazu passten auch die bereits nachgewiesenen Einflüsse seiner Liganden auf die Blasenfunktion von Hunden. Die hier vorgelegte Arbeit untersuchte zum ersten Mal die Expression des LHCGR mittels PCR und Immunhistochemie in humanen Harnblasen und Ureteren. Dabei löste sie sich von den sonst üblichen Vorstellungen einer Beziehung des Rezeptors zu Blasentumoren, Schwangerschaft oder Inkontinenz. Diagnose und Therapie von BPS/IC sind zur Zeit noch ständigen Wandlungen unterworfen und dabei entgehen viele Patienten der (frühen) Diagnosestellung und einer adäquaten Behandlung. Diese Studie sollte dazu beitragen neue Einblicke in die Pathophysiologie der Erkrankung zu erlangen, um eine kausale Therapie entwickeln zu können. Zukünftig könnten diese Ergebnisse dabei helfen die Anwendung einer sensitiven und vor allem spezifischen Diagnostik auf molekularer Ebene (mRNA - oder Proteinnachweis) zu ermöglichen.
10
Costa, Marcia Helena Soares. "Estudo da expressão dos receptores do peptídeo insulinotrópico dependente de glicose (GIPR) e do hormônio luteinizante (LHCGR) em tumores e hiperplasias do córtex adrenal." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-11092007-134837/.
Повний текст джерелаАнотація:
Introdução: Os receptores do peptídeo insulinotrópico dependente de glicose (GIPR) e do hormônio luteinizante (LHCGR) são receptores acoplados à proteína G com amplo padrão de expressão tecidual. A expressão anômala destes receptores tem sido descrita em casos de hiperplasia adrenal macronodular independente de ACTH (AIMAH) e em alguns adenomas, resultando em aumento da secreção hormonal (cortisol, andrógenos e aldosterona) pelo cortex adrenal. O papel destes receptores em outras formas de hiperplasia, como a doença adrenocortical nodular pigmentosa primária (PPNAD), aumento da adrenal associado à neoplasia endócrina múltipla tipo 1 (MEN1), e em carcinoma do córtex adrenal tem sido pouco investigado; sendo assim, considera-se relevante estudar a expressão destes receptores nos pacientes com tumores adrenocorticais esporádicos, nos pacientes com AIMAH, PPNAD e aumento adrenal associado à MEN1. Objetivos: 1) Caracterização molecular dos casos de neoplasia endócrina múltipla tipo 1 e PPNAD: pesquisa de mutações dos genes MEN1 e PRKAR1A e análise da perda de heterozigose (LOH) destes genes no tecido adrenal destes pacientes. 2) Quantificar a expressão do GIPR e do LHCGR em tecido adrenocortical normal, tumoral, hiperplásico e correlacionar a expressão destes com a classificação histológica dos tumores adrenocorticais. Pacientes: 55 pacientes (30 adultos) com tumores adrenocorticais (37 adenomas e 18 carcinomas); 7 pacientes com AIMAH, 4 com MEN1, 1 com PPNAD e tecidos controles (adrenal; testículo e pâncreas). Métodos: extração de DNA genômico, RNA e síntese de DNA complementar (cDNA); amplificação por PCR das regiões codificadoras dos genes MEN1 e PRKAR1A seguida por seqüenciamento automático. Pesquisa de LOH pela amplificação de microssatélites por PCR e análise pelo programa GeneScan. Quantificação da expressão do GIPR e do LHCGR por PCR em tempo real pelo método TaqMan e estudo de imunohistoquímica para GIPR nos tumores adrenocorticais. Resultados: identificação de 3 mutações (893+ 1G>A, W183X e A68fsX118) e dois polimorfirmos (S145S e D418D) no gene MEN1 e uma mutação (Y21X) no PRKAR1A. Ausência de LOH nos tecidos adrenais estudados. A expressão do GIPR e do LHCGR foi identificada em tecidos adrenais normais, tumorais e hiperplásicos. O nível de expressão do GIPR foi mais elevado nos tumores adrenocorticais malignos que nos benignos tanto no grupo pediátrico (mediana= 18,1 e 4,6, respectivamente; p <0,05), quanto no grupo adulto (mediana = 4,8 e 1,3 respectivamente; p <0,001). O nível de expressão do LHCGR, no grupo pediátrico, foi elevado tanto nos tumores benignos quanto nos malignos (mediana= 6,4 e 4,3, respectivamente). No grupo adulto os níveis de expressão deste receptor foram extremamente baixos nos tumores malignos em relação aos benignos (mediana= 0,06 e 2,3, respectivamente; p <0,001). A imunohistoquímica para o GIPR foi variável e não correlacionada à expressão do gene GIPR. Não houve diferença nos níveis de expressão do GIPR e do LHCGR nas hiperplasias do córtex adrenal. Conclusões: a presença de LOH e mutação em heterozigose composta do gene MEN1 e do PRKAR1A foram afastadas como mecanismos responsáveis pelo aumento adrenal tanto nos pacientes com MEN1 como no paciente com PPNAD. A hiperexpressão de GIPR está associada a malignidade nos tumores adrenocorticais nos grupos adulto e pediátrico e a baixa expressão de LHCGR está associada a malignidade nos tumores adrenocorticais somente no grupo adulto.Introduction: The glucose- dependent insulinotropic peptide receptor (GIPR) and luteinizing hormone receptor (LHCGR) are G-protein coupled receptors with a wide tissue expression pattern. The aberrant expression of these receptors has been described in cases of ACTH-independent macronodular adrenal hyperplasia (AIMAH) and in some adenomas, resulting in the increase of adrenal cortex hormonal secretion (cortisol, androgens and aldosterone). The role of these receptors in other forms of adrenocortical hyperplasia, such as primary pigmented nodular adrenocortical disease (PPNAD), adrenal enlargement associated with multiple endocrine neoplasia type 1 (MEN1), and adrenocortical carcinoma has been scarcely investigated. Thus, the study of the expression of these receptors in patients with sporadical adrenocortical tumors, AIMAH, PPNAD and adrenal enlargement associated to MEN1 was considered important. Objectives: 1) Molecular study in patients with multiple endocrine neoplasia type 1 and PPNAD: mutation screening of MEN1 and PRKAR1A genes and analysis of the loss of heterozygosis (LOH) of these genes in the adrenal lesions of these patients. 2) To quantify the GIPR and LHCGR expression, in normal, tumor and hyperplasic tissue and to correlate the expression of these receptors with the adrenocortical tumor histology. Patients: 55 patients (30 adults) with adrenocortical tumors (37 adenomas and 18 carcinomas); 7 patients with AIMAH, 4 with MEN1, 1 with PPNAD and control tissue (adrenal, testis and pancreas). Methods: Extraction of genomic DNA, RNA and synthesis of complementary DNA (cDNA); PCR-amplification of the coding regions of MEN1 and PRKAR1A, followed by direct sequencing. LOH study using polymorphic marker amplification by PCR and GeneScan software analysis. Quantification of GIPR and LHCGR expression using realtime PCR -TaqMan method and GIPR immunohistochemistry study in adrenocortical tumors. Results: Identification of 3 mutations (893+ 1G>A, W183X and A68fsX118) and two polymorphic alterations (S145S and D418D) in MEN1 and a mutation (Y21X) in the PRKAR1A gene; LOH was not identified in adrenal tissue. The GIPR and LHCGR expression was identified in normal, tumor and hyperplasic adrenal tissues; the GIPR expression level was more elevated in malignant tumors compared to benign tumors in pediatric (median = 18.1 and 4.6, respectively; p <0.05) and adult patients (median = 4.8 and 1.3 respectively; p <0.001). The LHCGR expression in pediatric patients was elevated in benign as well as in malignant tumors (median = 6.4 and 4.3, respectively). In the adult group, the expression level of these receptors was extremely low in malignant tumors in relation to benign ones (median = 0.06 and 2.3, respectively; p <0.001). The GIPR immunohistochemistry was variable and did not correlate with GIPR gene expression. No difference between GIPR and LHCGR expression levels was observed in the different forms of hyperplasia. Conclusions: The presence of LOH and mutations in compound heterozygosis of MEN1 and PRKAR1A genes were ruled out as the mechanisms responsible for the adrenal enlargement in patients with multiple endocrine neoplasia type 1. GIPR overexpression is associated with malignant adrenocortical tumors in the adult and pediatric patients and low LHCGR expression is associated with malignant adrenocortical tumors only in the adult patients.
Частини книг з теми "LHCSR1"
1
Pandit, Anjali, Tineke de Ruijter, Riekje Brandsma, Jaap Brouwer, Huub J. M. de Groot, and Willem J. de Grip. "Cell-Free Expression of the Lhcb1 Protein of Arabidopsis Thaliana." In Advanced Topics in Science and Technology in China, 110–12. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-32034-7_23.
Повний текст джерела
2
Klimmek, Frank, L. Horst Grimme, and Jürgen Knoetzel. "In Vitro Reconstitution of Barley LHCA1 and LHCA4, the Proteins of Photosystem I Antenna Subcomplex LHCI-730." In Photosynthesis: Mechanisms and Effects, 413–16. Dordrecht: Springer Netherlands, 1998. http://dx.doi.org/10.1007/978-94-011-3953-3_98.
Повний текст джерела
3
Bossmann, Björn, L. Horst Grimme, and Jürgen Knoetzel. "Spectral Properties of Long-Wavelength Chlorophylls in Barley Photosystem I Depend on Intimate Interaction Between LHCA1, LHCA4 and the Reaction Centre." In Photosynthesis: Mechanisms and Effects, 409–12. Dordrecht: Springer Netherlands, 1998. http://dx.doi.org/10.1007/978-94-011-3953-3_97.
Повний текст джерела
4
Aghdasi, M., S. Fattahi, and H. R. "Functional Analysis of LHCB1 in Arabidopsis Growth, Development and Photosynthetic Capacity." In Applied Photosynthesis. InTech, 2012. http://dx.doi.org/10.5772/26937.
Повний текст джерела
5
Gromoll, J., A. Richter-Unruh, and N. Kossack. "A Novel Exon within the LH/CG Receptor Gene as Transcriptional Regulator of LHCGR Signalling." In The Endocrine Society's 92nd Annual Meeting, June 19–22, 2010 - San Diego, OR21–2—OR21–2. Endocrine Society, 2010. http://dx.doi.org/10.1210/endo-meetings.2010.part3.or1.or21-2.
Повний текст джерелаТези доповідей конференцій з теми "LHCSR1"
1
de la Cruz Valbuena, Gabriel Jose, Franco Valduga De Almeida Camargo, Rocio Borrego Varillas, Federico Perozeni, Cosimo DaAndrea, Matteo Ballottari, and Giulio Cerullo. "Molecular Mechanism of Non-Photochemical Quenching in LHCSR3 Protein of Chlamydomonas Reindhartii." In 2019 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC). IEEE, 2019. http://dx.doi.org/10.1109/cleoe-eqec.2019.8872630.
Повний текст джерела
2
Yang, Haomiao, Mingxuan Yao, Zili Xu, and Baoshu Liu. "LHCSAS: A Lightweight and Highly-Compatible Solution for ADS-B Security." In 2017 IEEE Global Communications Conference (GLOBECOM 2017). IEEE, 2017. http://dx.doi.org/10.1109/glocom.2017.8254500.
Повний текст джерела
3
Kovalchuk, Svetlana, Anna Arkhipova, and Аrina Tagmazian. "Development of the Real-Time PCR method for detection of ss52050737 polymorphism of lhcgr gene in cattle." In Proceedings of the International Scientific and Practical Conference “Digital agriculture - development strategy” (ISPC 2019). Paris, France: Atlantis Press, 2019. http://dx.doi.org/10.2991/ispc-19.2019.78.
Повний текст джерела