Дисертації з теми "Calpain system"
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Janardhanan, Anitha C. "Gene expression of components of the calpain system m-calpain, [mu]-calpain and calpastatin in male and female broiler skeletal muscle /." Morgantown, W. Va. : [West Virginia University Libraries], 1999. http://etd.wvu.edu/templates/showETD.cfm?recnum=895.
Повний текст джерелаTitle from document title page. Document formatted into pages; contains vii, 93 p. : ill. (some col.) Includes abstract. Includes bibliographical references (p. 72-80).
Drouet, Saltos Domenica Elizabeth. "Calpain-Calpastatin System in Peripheral Nerve Myelination and Demyelination." Wright State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=wright1559220437439116.
Повний текст джерелаJones, Simon W. "Fibre-type specific expression of the calpain proteolytic system in skeletal muscle." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312237.
Повний текст джерелаDelgado, Eduardo Francisquine. "The calpain system and postmortem tenderization in ovine meat from callipyge and normal phenotypes." Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/288910.
Повний текст джерелаCataldo, Francesca. "Role of calpain in USP1 stability regulation and genome integrity maintenance." Doctoral thesis, Università degli studi di Trieste, 2012. http://hdl.handle.net/10077/7860.
Повний текст джерелаThe calpains are a family of intracellular cysteine proteases, among which the best studied isoforms, micro- (CAPN1) and milli-calpain (CAPN2), are heterodimers consisting of a catalytic subunit and a common regulatory subunit, CAPNS1, required for function. Calpain is involved in many processes important for cancer biology, such as autophagy, indeed in calpain-depleted cells autophagy is impaired, with a subsequent increase in apoptosis sensitivity. Calpain is also important in all the stages of the stress response. A proteomic approach was employed for the identification of novel CAPNS1 interacting proteins. Proteins immunoprecipitating with endogenous CAPNS1 in HT1080 cell lysates were analyzed by Mass Spectrometry. We identified novel partners among which the deubiquitinating enzyme USP1, a key regulator of the DNA damage response and genome integrity maintenance via its specific action on FANCD2, involved in DNA repair and protection from chromosome instability, and PCNA, involved in the regulation of translesion DNA synthesis (TLS), that bypasses DNA lesions with low stringency basepairing requirements. We performed co-IP assays in lysates of 293T cells and confirmed that the interaction was specific. Furhermore, we observed that calpain is able to bind a USP1 C-terminal deleted mutant, suggesting that USP1 first 523 aminoacids were sufficient for the binding. To understand what is the effect exerted by calpain upon USP1, we depleted calpain activity in a series of cell lines, and followed the fate of endogenous USP1. We transfected CAPNS1 specific siRNAs, or treated cells with a specific inhibitor of calpain, and we observed a strong decrease in USP1 protein levels. This effect should be at a post-transcriptional level, since any significant change in USP1 mRNA levels is detected. We also obtained the same result by transfecting a siRNA specific for CAPN1, the gene encoding for the catalytic subunit micro-calpain. Moreover, we studied the role of calpain in the PCNA-mediated switch between high fidelity replication and TLS upon UV irradiation. In mouse embryonic fibroblasts knockout for CAPNS1, USP1 downregulation is coupled to an increase in PCNA monoubiquitination. Moreover, CAPNS1-depleted U2OS cells showed an increase in the percentage of nuclei containing PCNA-induced foci upon UV irradiation. Since we demonstrated that calpain can modulate an important regulator of DNA damage response such as USP1, we investigated if calpain could have a role in genome integrity maintenance. CAPNS1 depleted cells showed a reduced rescue in DNA repair compared to control cells, suggesting that increased levels in PCNA monoubiquitination could lead to an increased amount of errore-prone TLS. Calpain plays an important role in autophagy, so we asked if USP1 degradation in absence of calpain activity could involve autophagic pathways. We first blocked macroautophagy by silencing ATG5, and we observed that USP1 was downregulated, suggesting that the depletion of ATG5 could lead to an increased activity of other degradation pathways. To impaire chaperone-mediated autophagy (CMA), we silenced a protein important for autophagosome formation, LAMP-2A. Also in this case we observed a decrease in USP1 protein levels, thus suggesting that USP1 is alternatively degraded by different pathways. However, we observed that USP1 is stabilized upon inhibition of lysosomal enzymes, suggesting that USP1 may be degraded in the lysosome. To better understand the mechanism by which calpain affect USP1 stability we search for an effect of calpain upon USP1 co-factor and activator UAF1/WDR48. CAPNS1-depleted cells showed WDR48 downregulation, but WDR48 overexpression only partially rescue USP1 protein levels in this cells. Furthermore, we provided evidences that calpain regulation of p35/p25 activator of Cdk5 can affect Cdh1 phosphorylation and thus APC/Cdh1 activity, leading to a regulation of USP1 stabilization. In conclusion, we identified USP1 as a novel interactor of calpain, and we found that calpain is important for USP1 stability, since in its absence USP1 is downregulated. The importance of this novel regulation is strengthened by the recent findings that unveiled a role of USP1 in maintenance of a mesenchymal stem cell program in osteosarcoma, and thus placing calpain in a crucial regulatory position for cancer development.
XXIV Ciclo
1983
Li, Liang. "The role of calpain-calpastatin system in in the SOD1G93A mouse model of amyotrophic lateral sclerosis." Thesis, University of Brighton, 2009. https://research.brighton.ac.uk/en/studentTheses/e0f03b52-5ddc-42cc-b769-ccde3e69e709.
Повний текст джерелаAmini, Mandana. "Analysis of Conditional Knock-out of Calpain Small Subunit, capns1, in Central Nervous System Development and Function." Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31360.
Повний текст джерелаKloock, Simon Johannes [Verfasser]. "Einfluss von VDAC1 auf das Calpain-System als mögliche therapeutische Option für Morbus Huntington / Simon Johannes Kloock." Tübingen : Universitätsbibliothek Tübingen, 2020. http://d-nb.info/1224882385/34.
Повний текст джерелаHoward, Benjamin. "Effects of Implanting Strategy and Zilpaterol Hydrochloride on the Calpain Proteolytic System in Sectioned Beef Steaks for Two Time Periods." Thesis, North Dakota State University, 2016. https://hdl.handle.net/10365/28128.
Повний текст джерелаLee, Hannah Yun Young. "Calcium homeostasis in lens transparency and the involmement of calpains in cataract." Lincoln University, 2006. http://hdl.handle.net/10182/1897.
Повний текст джерелаGrill, Mischala Ann. "Calpains in skeletal muscle: Generation of an inhibitory overexpression system and analysis of degradation in simulated microgravity." Diss., The University of Arizona, 2003. http://hdl.handle.net/10150/280476.
Повний текст джерелаKao, Chen-Yu. "Local and sustained delivery of hydrophobic drugs to the spinal cord with polyketal microparticles." Diss., Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/37304.
Повний текст джерелаCHUNG, TSUN-CHIH, and 鍾尊智. "Effect of Overexpression of Truncated Calpain Small Subunit on Calpain System in L8 myoblast." Thesis, 1999. http://ndltd.ncl.edu.tw/handle/58735383350385903530.
Повний текст джерела東海大學
畜產學系
87
The growth rate of skeletal muscle dependents on the rates of muscle protein synthesis and protein degradation. It was reported that calpains played an important role on the initiation of muscle protein degradation. The calpains depend on its calcium requirement can be grouped into - and m-calpain. Both and m-calpain contain two subunit, small subunit ( CS; 30KDa ) and large subunit ( CL; 80KDa ). The objectives of this study were to investigate the function of CS by expressing the autolysis form of CS in L8 myoblast. Rat post-autolysis small subunit ( 21KCS; 21KDa ) cDNA was amplified by polymerase chain reaction ( PCR ). The cDNA ( 577bp ) then was inserted into pMAMneo-SV40 ( pSV ) vector. The new plasmid is referred to pMAMneo-SV40-Small subunit ( pSV-SS ). The plasmid pSV and pSV-SS were transfected into L8 myoblasts, respectively. Then the single cloning was selected by G418 ( 300g/ ml ) containing medium. After selection, the transfected cell were analyzed by PCR using Neor primer against the genomic DNA and stable cloning cell line L8-Neo, SS1, SS2 and SS3 were established. CS mRNA were analyzed by Reverse transcription polymerase chain reaction ( RT-PCR ) in transfected and control cells using primer 21K-1 and oligo-dT. The data indicated that SS2 and SS3 had expression of exogenous CS mRNA ( 21KCS mRNA ), however, SS1 did not express the exogenous CS mRNA. In addition, and m-calpain were analyzed by Western blot in total and membrane protein. In analysis of total protein, the results showed that the protein concentration of - calpain in SS2 and SS3 were 15.7% and 17.3% higher than control ( L8-Neo ), respectively. The protein concentration of m-calpain in SS2 and SS3 were 23.3% and 16.6% higher than control ( L8-Neo ), respectively. In addition, SS3 and control ( L8-Neo ) were analyzed by immunoprecipitation to detect the stability of calpain. The data indicated that the stability of -calpain in SS3 was 36.3 hours higher than control ( 31.9hours ). The stability of -calpain was 40.5 hours higher than control ( 36.3hours ). In analysis of membrane calpain concentration, the transfected cells ( SS1、SS2 and SS3 ) and control cell ( L8-Neo ) have no significant difference by expression of exogenous CS. Also, there is no different in total protein degradation between transfected cells and control cells. These results imply that expression of exogenous 21KCS can increase the protein level of - and m-calpain and increase the stability of calpains. The result indicated that 21KCS effect on translation level but not on transcription level. On the pther hand, 21KCS can not improve the opportunity to translocte to the membrane or change the rate of protein degradation in myoblast of rat.
前本, 佑樹, and Yuki Maemoto. "Biochemical Studies on Calpain-7 in the ESCRT System." Thesis, 2014. http://hdl.handle.net/2237/20255.
Повний текст джерелаBall, Chad Geoffrey. "Exercise-induced muscle damage : role of the calpain-calpastatin system in skeletal muscle myofibrillar protein composition." Thesis, 1998. http://hdl.handle.net/2429/7735.
Повний текст джерелаXiao, Ying-Yi. "Regulation of skeletal muscle protein degradation by u-calpain and development of a skeletal muscle-specific inducible expression system." Thesis, 2001. http://hdl.handle.net/1957/32264.
Повний текст джерелаGraduation date: 2002
Spormann, Johannes. "Kalzium Kanal Blockade limitiert die Transkription, Translation und funktionelle Aufregulation des kardialen Calpain Systems nach Myokardinfarkt." 2004. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=014731125&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
Повний текст джерелаSalazar, Ivan Lalanda. "Regulation of the Ubiquitin-Proteasome System in brain ischemia: impact on the neuronal proteome." Doctoral thesis, 2017. http://hdl.handle.net/10316/33156.
Повний текст джерелаIschemic stroke is characterized by a decrease in oxygen supply to the brain with a consequent impairment in the metabolic activity. The sudden decrease in the levels of ATP affect the balance between excitatory and inhibitory neurotransmission, and the overactivation of glutamate receptors leads to neuronal death (excitotoxicity). Under these conditions, the [Ca2+]i overload to the postsynaptic cell induces the activation of calpains, a group calcium-dependent proteases that regulate the function of many substrate proteins through limited proteolysis. In parallel to calpain activation, the Ubiquitin-Proteasome System (UPS), one of the major protein degradation systems in the cells, which also regulate several key and physiological functions, was also shown to be downregulated under energy-depriving conditions. However, how these two proteolytic systems are interconnected under ischemic conditions is currently unknown. Multiple lines of evidences suggest that proteasome inhibition is beneficial in in vivo models of transient/global ischemia by halting the inflammatory process. However, proteasome activation may also be a powerful tool to prevent cell demise in acute brain injury, and in other disorders of the nervous system, by enhancing the degradation of damaged proteins. In this work, we characterized the alterations in the subcellular distribution of the proteasome in cultured neurons subjected to ischemic conditions, and investigated the mechanisms contributing to the downregulation of the proteasome under the same conditions. In particular, we focused on the putative effects of calpains on the proteasome components, and the impact of the proteasome in neuronal demise. We found that Oxygen-Glucose Deprivation (OGD), a well-known in vitro model mimicking transient global ischemia in cultured neurons, had a differential effect on the dendritic distribution of the proteasome proteins PSMA2 and Rpt6, used as markers of the 20S and 19S proteasome particles, respectively. Non-denaturing polyacrylamide gel electrophoresis (PAGE) followed by immunoblotting with antibodies against the PSMA2 and Rpt6 also showed a disassembly of the proteasome in cortical neurons subjected to in vitro ischemia, further indicating that this is an appropriate model to study the regulation of the proteasome under ischemic conditions. OGD was also found to enhance calpain activity (assessed by the cleavage of its substrate spectrin) and had the opposite effect on the activity of the proteasome (determined with a fluorogenic substrate). In contrast with the biochemical changes often associated with inhibition of the proteasome, polyubiquitin conjugates were found to be reduced in cortical neurons subjected to OGD, while no changes were detected in free ubiquitin levels. Two non-related assays were used aiming at identifying which subunits of the 19S proteasome may be cleaved by calpains: (i) cleavage of endogenous proteins in cortical neurons subjected to OGD and (ii) cleavage of green fluorescent protein (GFP) fusion proteins with proteasome subunits in extracts obtained from HEK293t cells incubated with recombinant calpain. We found that the ubiquitin acceptor Rpn10, together with Rpt3 and Rpt5 are calpain substrates, and this may also be the case for Rpt1 and Rpn3. Finally, here we report that inhibition of USP14, a deubiquitinating enzyme (DUB) associated with the 26S proteasome, provides robust neuroprotection to cerebrocortical neurons subjected to OGD. USP14 inhibition was previously shown to increase the proteolytic activity of the proteasome towards specific substrates, suggesting that increasing degradation of canonical proteasome substrates is sufficient to prevent cell death. Importantly, incubation of cortical neurons with IU1, the USP14 inhibitor, prevented the OGD-induced activation of calpains, but the underlying mechanism remains to be investigated. Taken together, the results show that OGD induces hypofunction of the proteasome, alongside with an increased activity of calpain against proteasome resident subunits. The mechanism proposed here conciliates the calpain-mediated cleavage of proteasome subunits with the observed disassembly under ischemic conditions. Enhancing the activity of the proteasome prevents cell demise associated with OGD in cultured cerebrocortical neurons, and may represent a novel therapeutic target to restore the deficits observed after stroke.
O acidente vascular cerebral (AVC) é caracterizado pela diminuição da irrigação sanguínea ao nível do cérebro, com consequente alteração da atividade metabólica. O súbito decréscimo dos níveis de ATP afeta toda a neurotransmissão excitatória e inibitória, e a sobreactivação dos recetores para o glutamato levam à morte neuronal (excitotoxicidade). Nestas condições, o aumento excessivo da [Ca2+]i na célula pós-sináptica é responsável por ativar as calpaínas, um grupo de proteases reguladas por este ião que controla a função de inúmeras proteínas na célula através de proteólise limitada. Paralelamente à ativação das calpaínas, o Sistema Ubiquitina-Proteassoma (UPS), o principal sistema de degradação proteico existente nas células, que tem um papel chave na regulação de vários processos biológicos, encontra-se inibido em condições de deficit de energia na célula. No entanto, a forma como estes dois sistemas proteolíticos interagem não é de todo conhecido. Várias evidências sugerem que a inibição do proteassoma tem um papel protetor em modelos in vivo de isquémia transiente/global, através da inibição do processo inflamatório. No entanto, a ativação do proteassoma também pode ser benéfica na prevenção da morte celular em várias agressões do tipo agudo/traumáticas ao nível do cérebro, bem como em doenças neurodegenerativas, através do aumento da degradação de proteínas danificadas. Neste trabalho, caracterizámos a alteração na distribuição subcelular do proteassoma em neurónios submetidos a isquémia in vitro, bem como os mecanismos que contribuem para a diminuição da atividade do proteassoma nas mesmas condições. Focámo-nos em particular nos efeitos putativos das calpaínas sobre componentes do proteassoma, bem como no impacto do UPS na morte celular. Observou-se que a deprivação de oxigénio e glucose (OGD) em neurónios em cultura, um modelo in vitro que mimetiza o efeito transitório da isquémia global, tem um efeito diferencial na distribuição dendrítica das proteínas PSMA2 e Rpt6, duas subunidades do proteassoma vulgarmente usadas como marcadores do 20S e do 19S, respetivamente. Eletroforese em géis de poliacrilamida em condições não desnaturantes, seguido de imunoblot contra as proteínas PSMA2 e Rpt6, revelou que o proteassoma é desmontado em neurónios corticais submetidos ao modelo in vitro de isquémia cerebral, indicando que se trata de um modelo apropriado para estudar a regulação do proteassoma nestas condições. A incubação transitória de neurónios em cultura na ausência de oxigénio e glucose induziu a ativação de calpaínas (avaliado através da análise da clivagem da espectrina) e alterou de forma oposta a atividade do proteassoma (determinado através de um ensaio fluorogénico). No entanto, ao contrário das alterações bioquímicas observadas após inibição química do proteassoma, os níveis de proteínas conjugadas com cadeias de poliubiquitina diminuiu em neurónios corticais em cultura submetidos a OGD, não tendo sido observadas quaisquer alterações nos níveis da ubiquitina livre. Com o objetivo de identificar que proteínas associadas ao 19S podem ser clivadas pelas calpainas, usámos dois ensaios distintos: (i) análise da clivagem de proteínas endógenas em neurónios corticais em cultura submetidos a OGD e (ii) clivagem de proteínas de fusão contendo a sequência de aminoácidos de subunidades do proteassoma associada a GFP (green fluorescent protein) em extratos de células HEK293t incubados com calpaína recombinante. Nestes ensaios observou-se a clivagem do recetor para a ubiquitina Rpn10, juntamente com a proteína Rpt3, sendo que o mesmo poderá também acontecer para as proteínas Rpt1 e Rpn3. Neste trabalho observámos também que a inibição da USP14, uma enzima de desubiquitinação (DUB) associada ao proteassoma 26S, tem um efeito protetor significativo em neurónios corticais submetidos a OGD. Estudos prévios mostraram que a inibição da USP14 estimula a capacidade proteolítica do proteassoma sobre substratos específicos, sugerindo que o aumento da degradação dos seus substratos canónicos é suficiente para prevenir a morte neuronal. Observou-se também que a incubação de neurónios corticais com o inibidor USP14 impede a ativação de calpaínas em resultado da incubação em condições de OGD. No entanto, os mecanismos responsáveis pela inibição das calpaínas nestas condições não estão esclarecidos. Em conjunto, os resultados obtidos mostram que a atividade do proteassoma se encontra diminuído em condições de OGD, bem como a clivagem de proteínas associadas ao mesmo por parte das calpaínas. O mecanismo aqui proposto concilia a clivagem de proteínas associadas ao proteassoma com a sua desmontagem em condições de isquémia. O aumento da atividade do proteassoma preveniu a morte de neurónios corticais em cultura submetidos a OGD, e pode representar uma nova estratégia terapêutica na recuperação do tecido nervoso após um AVC.