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Czerwinski, Eric Paul. "Two Proteins Containing Tandem DIII Domains, Calpain 10 and Dictyostelium Cpl, are Involved in Cytoskeletal Regulation". Connect to Online Resource-OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=mco1193689816.
Pełny tekst źródła"In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Sciences." Title from title page of PDF document. Bibliography: p. 117-147.
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.
Pełny tekst źródłaTitle from document title page. Document formatted into pages; contains vii, 93 p. : ill. (some col.) Includes abstract. Includes bibliographical references (p. 72-80).
Fernández-Montalván, Amaury Ernesto. "Structural requirements for activation and membrane binding of human m-calpain [mu-calpain]". [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=973390123.
Pełny tekst źródłaSchroeder, Ewald. "Structural studies of #mu#-calpain, a novel calpain substrate, and a papain-leupeptin complex". Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386677.
Pełny tekst źródłaHuang, Xinhua. "DIII Domain of Calpain 10 and Cpl Towards an Understanding of Calpain 10 Function". University of Toledo Health Science Campus / OhioLINK, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=mco1096641027.
Pełny tekst źródłaHuang, Xinhua. "DIII domain of calpain 10 and Cpl towards an understanding of calpain 10 function /". Connect to full-text via OhioLINK ETD Center, 2003. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=mco1096641027.
Pełny tekst źródła"In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Medical Sciences." Major advisor: Ronald Mellgren. Includes abstract. Document formatted into pages: iv, 126 p. Title from title page of PDF document. Includes bibliographical references (p. 92-124).
Rose, Robert Edward. "Calpain and lipopolysaccharide mediated hepatitis". Thesis, [College Station, Tex. : Texas A&M University, 2006. http://hdl.handle.net/1969.1/ETD-TAMU-1806.
Pełny tekst źródłaPlammootil, Salma Martha. "Mutationen im Calpain-3-Gen". [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=973536306.
Pełny tekst źródłaDouillard, Aymeric. "Implication des calpaïnes lors d'un remodelage musculaire induit par un traitement chronique au clenbutérol". Thesis, Montpellier 1, 2011. http://www.theses.fr/2011MON14001/document.
Pełny tekst źródłaTo fight doping in an effective manner, it is essential to understand the mechanisms leading to muscle remodeling. For this purpose we analyzed the effects of clenbuterol, on muscle remodeling and various associated signaling pathways. We were particularly interested with the calpain system which has often been associated with muscle remodeling phenomena, mainly in models of atrophy. We have shown that an early calpain system solicitation during chronic treatment with clenbuterol in rats was associated with a phenotypic conversion in the Soleus and EDL muscles and hypertrophy in the EDL muscle. We then inhibited the activity of calpains with a parallel clenbuterol treatment. The muscles with a reduced activity of calpain and treated with clenbuterol did not develop muscle remodeling. These initial results reinforce the idea of an involvement of calpain in the muscle remodeling induced by chronic treatment with clenbuterol
Arthur, John Simon Campbell. "Regulation of m-calpain by phospholipids". Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240569.
Pełny tekst źródłaJoshi, Aashish. "SUBSTRATE AND REGULATION OF MITOCHONDRIAL μ-CALPAIN". UKnowledge, 2009. http://uknowledge.uky.edu/gradschool_diss/80.
Pełny tekst źródłaChen, Hongyuan. "Design, synthesis and testing of calpain inhibitors for the treatment of cataract". Thesis, University of Canterbury. Chemistry, 2007. http://hdl.handle.net/10092/1405.
Pełny tekst źródłaSingh, Ranjana. "CALPAIN 5: A NON-CLASSICAL CALPAIN HIGHLY EXPRESSED IN THE CNS AND LOCALIZED TO MITOCHONDRIA AND NUCLEAR PML BODIES". UKnowledge, 2014. http://uknowledge.uky.edu/neurobio_etds/9.
Pełny tekst źródłaFraser-Smith, Emma Louise. "Characterizing the Catalytic Action of μ-Calpain on Myofibrillar Protein Structure". The University of Waikato, 2006. http://hdl.handle.net/10289/2253.
Pełny tekst źródłaSazili, Awis Qurni. "Calpastatin and meat tenderness in sheep and cattle". Thesis, University of Nottingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273257.
Pełny tekst źródłaIshak, Reezal. "Calpain-1 : investigating its role in murine neutrophils". Thesis, Cardiff University, 2012. http://orca.cf.ac.uk/37448/.
Pełny tekst źródłaOlego-Fernandez, S. "A calpain-like multigene family in Trypanosoma brucei". Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:5256ea6f-4da0-4d42-b77c-a0d2da6f3af2.
Pełny tekst źródłaZhang, Siwei. "Calpain in ovarian cancer progression and chemotherapeutic response". Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/51279/.
Pełny tekst źródłaWan, Feng. "[Rôle du sytème calpaïne /calpastatine dans le remodelage cardiovasculaire]". Thesis, Paris Est, 2013. http://www.theses.fr/2013PEST0067.
Pełny tekst źródłaTargeting the Calpain/Calpastatin System to Protect against Hypoxia-induced Pulmonary Hypertension in Mice. Calpain knockout mice exhibited protective effects against hypoxia-induced PH. Our aim was to study the role of the calpain/calpastatin system on PH development in mice. To this end, we used mice ubiquitously overexpressing intracellular calpastatin (cast) under the control of a CMV promoter (CMV-cast) to explore the effects of intracellular calpains. We also used mice overexpressing extracellular calpastatin under the control of a CRP (C-reactive protein) promoter (CRP-cast) to explore the effect of extracellular calpains. Finally, we examined the effects of treatment with PD150606, an inhibitor of calpain, in WT mice exposed to hypoxia and in SM22-5HTT+ mice with spontaneous PH. During time-course of hypoxia, we found that calpain and calpastatin protein levels increased immediately after hypoxic exposure. Calpain protein levels then peaked on day 8 and remained elevated until day 18 in hypoxic WT mice; however, calpastatin protein levels increased from day 1 to day 3, and returned to basal level until day 18. Both intra- and extra-cellular calpain activities were upregulated gradually and peaked on days 8, and still markedly remained in high levels until day 18 in hypoxic WT mice. By using immunofluorescence, we found that increased calpains were predominantly colocalized with α-SMA positive pulmonary vascular SMCs. In CMV-cast mice, intracellular calpastatin overexpression successfully attenuated PH development. In CMV-cast mice, calpastatin protein levels remained higher than those in WT mice at all time points of hypoxia. The higher calpastatin protein levels in CMV-cast mice did significantly prevent an increase in calpain protein levels and calpain intra- and extra-cellular activities during hypoxia. After 18 days hypoxia, CRP-cast mice exhibited less PH severity. Moreover, extracellular calpastatin overexpression showed similar effects as intracellular calpastatin overexpression. Treatment with PD150606 induced an additional protective effect in hypoxic WT mice but not CMV-cast and CRP-cast mice. In SM22-5HTT+ mice, lung calpastatin and calpain proteins as well as calpain intra- and extra-cellular activities were significantly increased. PD150606 did not alter lung tissue calpastatin. However, it significantly decreased calpain protein levels as well as calpain intra- and extra-cellular activities. In summary, our present results demonstrate that calpain inhibition prevents PH development. Either increasing extracellular calpastatin or increasing both extra- and intra-cellular calpastatin is efficient to attenuate PH. Treatment with PD150606 which inhibits both extra- and intra-cellular calpain activities may be useful in teh setting of PH
Hewitt, Kimberley E. "The role of calpain in excitotoxic neuronal cell death". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0017/NQ46523.pdf.
Pełny tekst źródłaAdams, Sarah Elizabeth. "The synthesis and evaluation of novel calpain-I inhibitors". Thesis, Cardiff University, 2013. http://orca.cf.ac.uk/53271/.
Pełny tekst źródłaChen, Hongyuan. "Development of macrocyclic β-strand calpain cysteine protease inhibitors". Thesis, University of Canterbury. Chemistry, 2011. http://hdl.handle.net/10092/5582.
Pełny tekst źródłaNorton, Luke. "Calpain-10 and insulin resistance in human skeletal muscle". Thesis, University of Nottingham, 2007. http://eprints.nottingham.ac.uk/11536/.
Pełny tekst źródłaParr, Timothy. "Calpain proteinase mRNA and beta-agonist induced muscle growth". Thesis, University of Nottingham, 1991. http://eprints.nottingham.ac.uk/11445/.
Pełny tekst źródłaLiu, Wen. "The characterisation of calpain-like proteins in Trypanosoma brucei". Thesis, University of Hull, 2010. http://hydra.hull.ac.uk/resources/hull:6899.
Pełny tekst źródłaJoyce, Peter. "Characterisation of the atypical calpain family of C elegans". Thesis, University of Bristol, 2008. http://hdl.handle.net/1983/fd3f92bf-ab35-4564-84d8-f36227fc0640.
Pełny tekst źródłaDrouet, 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.
Pełny tekst źródłaRedpath, Gregory. "Calpain cleavage and subcellular characterisation of the ferlin family". Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/14278.
Pełny tekst źródłaRobilotto, Anthony T. "Calpain activation following cryopreservation an initial investigation into their roles in cell death and cell adhesion /". Diss., Online access via UMI:, 2005. http://wwwlib.umi.com/dissertations/fullcit/1425587.
Pełny tekst źródłaKlanchantra, Mutita. "Design and synthesis of beta-strand conformationally constrained calpain inhibitors for cataract treatment via metathesis ring closure". Thesis, University of Canterbury. Chemistry, 2006. http://hdl.handle.net/10092/1609.
Pełny tekst źródłaKim, Hyun Woo. "Characterization of genes involved in molting and limb regeneration in land crab, Gecarcinus lateralis". Access citation, abstract and download form; downloadable file 6.77 Mb, 2004. http://wwwlib.umi.com/dissertations/fullcit/3131680.
Pełny tekst źródłaHanouna, Guillaume. "Rôle des calpaïnes dans le vieillissement et la réponse anti-tumorale". Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066385/document.
Pełny tekst źródłaCalpain 1 and 2 are cysteine proteases and calpastatin is their natural inhibitor. Calpains and calpastatin are ubiquitous. Calpains are involved in inflammatory response development via activation by partial proteolysis of several substrates (NF-kappaB activation by I-kappaBalpha cleavage, remodeling of inflammatory cells cytoskeleton, cleavage of chaperone protein HSP90 ... ). It has been previously shown that calpains promote neuronal aging. We have shown in a mouse model that inhibition of calpain by calpastatin overexpression limits renal and vascular aging. The inflammation associated with aging or "inflammaging" is considerably reduced by specific inhibition of calpain. This is due, at least in part, to calpain effect on production of pro-inflammatory cytokines and in maturation of interleukin-1 alpha. If intracellular calpains are pro-inflammatory, secreted calpains have an anti-inflammatory effect via cleavage of TLR2. Calpains can indeed be excreted out of the cells via the transporter ABCA1. In the context of a mouse model of melanoma, we have shown that inhibition of extracellular calpain by only extracellular calpastatin overexpression preserves TLR2 and thus limit the progression of the tumor.Calpains intra- and extracellular are major mediators of inflammatory response and modulate the "inflammaging" and the anti-tumor immune response
Vanhooser, Lisa M. "Engineering Calpastatin to Develop a Sensor to Detect Active Calpain". Fogler Library, University of Maine, 2006. http://www.library.umaine.edu/theses/pdf/VanhooserLM2006.pdf.
Pełny tekst źródłaNakagawa, Yasuaki. "Calcium-Dependent Neutral Proteinase(Calpain)in Fracture Healing of Rats". Kyoto University, 1994. http://hdl.handle.net/2433/168857.
Pełny tekst źródłaKyoto University (京都大学)
0048
新制・課程博士
博士(医学)
甲第5555号
医博第1525号
新制||医||577(附属図書館)
UT51-94-C13
京都大学大学院医学研究科外科系専攻
(主査)教授 畑中 正一, 教授 岡 正典, 教授 山室 隆夫
学位規則第4条第1項該当
Davis, Benjamin. "Genetic and Functional Analysis of Calpain-14 in Eosinophilic Esophagitis". University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1447688593.
Pełny tekst źródłaPasalic, Dario. "No Calpain, No Gain: Newly Developed Procedures for the Separation and Characterization of The Calpain Family of Proteins in Human Dystrophic and Non-dystophic Muscle". Thesis, The University of Arizona, 2010. http://hdl.handle.net/10150/146022.
Pełny tekst źródłaMazon, Madeline Rezende. "Efeitos da Imunocastração e de agonistas beta-adrenérgicos sobre a qualidade da carne de bovinos". Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/74/74131/tde-18052016-095207/.
Pełny tekst źródłaThe Beta adrenergic agonist (βAA) are knowed for increase muscle hypertrophy and lipolysis, in this case on way for decrease the lipolysis effect is use the immunocastration. The objective of this research was evaluated the effect of βAA and immunocastration on meat quality of Nellore . Ninety-six Nellore were fed in this trial; half of the animals (n = 48) received one dose of immunocastration vaccine on d 0, and received another dose at d 30. The other half of animals (n = 48) received no vaccine. Animals were fed with a standard diet consisting of 24% forage and 76% concentrate for 70 d. After 70 d of the standard diet, animals were divided into three groups, and were fed 30 d with one of the following diets: CON - standard diet used in the previous phase, without the addition of βAA; ZIL - standard diet plus 80 mg/d Zilpaterol hydrochloride; RAC - standard diet plus 300 mg/d Ractopamine hydrochloride. After this period, animals were harvested and the Longissimus dorsi sample were colleted to evaluate meat quality, total lipid content, fatty acid profile, consumer sensory analysis, muscle morfometric profile, genes expression of calpain and calpastatin and sarcomere length. For almost of characteristics evaluated, were not observed interactions between treatments. The effect of sexual condition, imunocastrated animals showed higher intensity of color L, a and b, total lipidics, oleic, palmitic and total monounsaturated acids and more frequency for oxidative fibers (FO) and glycolytic fibers (FG) in relation at noncastrated. However, non-castrated animals had a tendency to show a meat tender in sensory analysis and more frequency of oxidative-glicolytics fibres (FOG) in relation to imunocastrated. The βAA effect, ZIL group showed a meat less tender, higher concentrations of heptadecanoic, linoleic, araquidic acids, C20:3 N6C8C11C14, ômega 6, higher frequency for FO and less for FG than RAC and CON group. Animals of CON and ZIL group showed more FO area than RAC group, while for the FOG, animals from COM group showed more area than animals from RAC and ZIL group. In the sensory analysis, RAC and ZIL group received lower grades for tenderness and global quality in relation to COM group. Was no observed effect of sexual condition and βAA for genes expressions and sarcomere length. As conclusion, sexual condition and βAA affected the meat quality, fatty acid profile, muscle fibers, but not affect genes expression and sarcomere lenght.
Millar, Tarek Lawson. "Synthesis and evaluation of CA clan cysteine inhibitors". Thesis, University of Canterbury. Chemistry, 2008. http://hdl.handle.net/10092/1911.
Pełny tekst źródłaStuart, Blair Gibb. "Molecular Modelling for Enzyme Inhibition: A Search for a New Treatment for Cataract and New Antimicrobials and Herbicides". Thesis, University of Canterbury. Chemistry, 2010. http://hdl.handle.net/10092/4551.
Pełny tekst źródłaDraper, Kati Elizabeth. "Increased structure-bound proteolytic activity in maturing dystrophic skeletal muscle". Thesis, Virginia Tech, 2004. http://hdl.handle.net/10919/31735.
Pełny tekst źródłaMaster of Science
Wang, Qiong. "The activity and content of calpains in maturing dystrophic muscle membranes". Thesis, Virginia Tech, 2005. http://hdl.handle.net/10919/42729.
Pełny tekst źródłaMaster of Science
Sun, ChunHui. "Régulation des réponses calciques et de la cytotoxicité par l’effecteur de type III IpgD durant l’invasion des cellules épithéliales par Shigella". Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS179.
Pełny tekst źródłaShigella, the agent of bacillary dysentery, invades colonic epithelial cells where it disseminates causing an intense inflammation and tissue destruction. To efficiently promote infection, Shigella injects virulence effectors via a type III secretion system (T3SS) into host cell to divert processes involved in cytoskeletal rearrangements and processes regulating inflammatory signals or tissue integrity. Among the Shigella T3SS effectors, IpgD acts as a phosphatidylinositol (PI) (4, 5) bisphosphate phosphatase, which dephosphorylates PI (4,5) P2 to generate PI(5)P. IpgD-mediated hydrolysis of PI (4, 5) P2 favors actin polymerization during cell invasion and negatively regulates the migration of T cells. PI(5)P produced by IpgD was also shown to up-regulate the PI3K/AKT cell survival pathway and recycling of the Epidermal Growth Factor receptor. My project thesis focuses on the role of IpgD in the control of calcium responses during Shigella infection. We show that that IpgD is responsible for a decrease in the recruitment of inositol-triphosphate (InsP3) receptors at invasion sites. Ca2+-imaging experiments indicate that during the early stages of bacterial invasion, IpgD favors the elicitation of local Ca2+responses at Shigella invasion sites, and limits the induction of global Ca2+ responses. Fliuorescence Recovery After Photobleaching (FRAP) experiments indicate that actin foci induced by the ipgD mutant show faster diffusion kinetics than those in foci induced by WT. Modeling studies support the notion that the local decrease in InsP3 levels and of its diffusion kinetics triggered by IpgD at entry sites accounted for the modulation of local to global Ca2+ responses during Shigella invasion. We show that over prolonged infection kinetics, IpgD inhibits InsP3-dependent global Ca2+ responses induced by Shigella or agonists. IpgD-mediated inhibition of Ca2+ signals delays the activation of calpain, the degradation of the focal adhesion protein talin, and cell death during bacterial intracellular replication. Our results provide evidence that IpgD is a critical T3SS effector of Shigella regulating the transition from local to global Ca2+ signals, and preserving cells from death linked to loss of adhesion
Allcock, Stephen M. J. "Interactions between calpain proteases #beta#-adrenergic receptor and skeletal muscle growth". Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.358286.
Pełny tekst źródłaLiu, Zhao. "PALMITATE INDUCED ENDOTHELIAL DYSFUNCTION: THE ROLE OF CALPAIN, AMPK AND ENOS". Master's thesis, Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/288932.
Pełny tekst źródłaM.S.
Obesity is a serious health problem worldwide. Consumption of fat rich food is a common cause of obesity. Some of the food components (i.e. saturated free fatty acids (SFAs)) have been identified as inflammatory inducers (Egger G at al., 2010). After a meal, absorbed free fatty acids (FFAs) will be stored in the liver and adipose tissue. On the luminal surfaces of endothelium in adipose tissue microcirculation, lipoprotein lipase hydrolyses absorbed triglycerides into FFAs. Then, in order to be available for adipocyte storage, FFAs have to cross the capillary endothelium barrier, which connected by tight junctions (Stremmel W et al., 2001). Increased leukocyte infiltration is a featured sign of adipose tissue inflammation found in obesity. Endothelial adhesion molecules up-regulation contributes to leukocyte infiltration during inflammation. Some clinical data suggested an increase of leukocyte-endothelium interaction in healthy volunteers after ingestion of high-fat meals (Shimabukuro M et al., 2007). Other lab results also showed that neutrophil infiltration occurred at a very early stage with high-fat feeding in mice (Talukdar S et al., 2012). However, the detailed mechanism of the above phenomena is still unknown. This thesis provides exciting preliminary data which will guide the further study in this area. First of all, we successfully established a stable protocol that CD31 antibody conjugated microbeads were used to isolate primary microvascular endothelial cells from fresh mice lung tissue. After second sorting, CD31+ cells reach 83.3% by FACS analysis. Previous literatures showed that FFAs activate recruitment of inflammatory cells through up-regulation of endothelial adhesion molecules via reduced eNOS derived eNO production (Rizzo NO et al., 2010; Davenpeck KL et al., 1994; Ahluwalia A et al., 2004). In this thesis, it was found that SFAs palmitate exposure dose dependently reduced endothelial AMPK thr172 and eNOS ser1177 phosphorylation by western blot. Moreover, our study demonstrated that endothelial calpain, a calcium dependent protease associated with endothelial dysfunction, was activated by palmitate, specifically its μ-calpain isoform. Altogether, these data suggested that a new role of calpain as a key mediator of palmitate induced endothelial dysfunction and indicated both AMPK and eNOS1177 phosphorylation contribute to this pathological process. Further investigations are still needed to explore connections among those molecules. This thesis may also lead to a novel way of clinical treatment for the obese related vascular diseases.
Temple University--Theses
Cataldo, 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.
Pełny tekst źródłaThe 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
MARCASSA, ELENA. "Dissection of the role of calpain in the regulation of autophagy". Doctoral thesis, Università degli Studi di Trieste, 2016. http://hdl.handle.net/11368/2908036.
Pełny tekst źródłaNettersheim, Jo-Ann. "Interplay between the translesion DNA polymerase η and the calpain system". Electronic Thesis or Diss., Strasbourg, 2020. http://www.theses.fr/2020STRAJ078.
Pełny tekst źródłaCells are constantly exposed to DNA damaging agents causing lesions, which are repaired by a range of DNA repair pathways. If DNA damages prevail during replication, they can cause replication fork breakdowns and mutations. One mechanism to prevent this is the translesion synthesis (TLS). Pol η is a translesion DNA polymerase which is capable to circumvent UV-induced lesions, to be repaired at a later time. However, pol η is error prone on non-damaged DNA and, therefore, needs to be tightly regulated. This thesis present an interaction between pol η and CAPNS1 and our investigation of its role in regulating pol η. CAPNS1 is the small subunit of the calcium dependent calpain 1 and 2. We demonstrate that CAPNS1 is colocalized with pol η in the nucleus and calpain 1/2 can cleave pol η in vitro and in vivo. The proteolysis of pol η is found to occur at position 465 leading to a truncated protein encompassing the catalytic domain and the PIP1 motif. Interestingly, inhibition of calpain leads to a perturbed pol η foci formation and decreased cell survival. Taken together, these results suggest an important positive role for calpain in pol η dependent TLS
Andrique, Caroline. "La calpaine- 6 identifie et maintient la population de cellules souches des necones osseux en contrôlant les processus d'autophagie et de sénescence". Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC306/document.
Pełny tekst źródłaCancer stem cells contribute to sarcoma development, but lack of specific markers prevents their characterization and the possibility of targeting. We used the regulatory sequence of calpain-6 in reporter constructions to identify calpain-6–expressing cells. These cells were tumor-initiating cells and behaved like stem cells at the apex of the cellular hierarchy. Calpain-6 expression depended on the stem-cell transcription network that involves Oct4, Nanog, and Sox2 and was activated by hypoxia. Calpain-6 knockdown blocked tumor development and induced depletion of sarcoma stem cells. Calpain-6 was inversely associated with expression of senescence markers but was associated with a dynamic autophagy flux. Calpain-6 knockdown induced cell entry into senescence and suppressed autophagy flux. Our results reveal that calpain-6 identifies sarcoma stem-cell and plays an important role as a regulator of cancer cell fate driving a switch between autophagy and senescence. Calpain-6 may be a promising therapeutic target to eradicate sarcoma stem cells
Carvalho, Minos Esperândio. "Caracterização da freqüência de polimorfismos em genes ligados à maciez da carne em bovinos da raça Nelore". Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/74/74131/tde-23062008-082501/.
Pełny tekst źródłaThe objective of this study was to evaluate the potential utilization of molecular markers on candidate calpain and calpastati n genes as an auxiliary tool for breeding programs on traits related to growth and meat tenderness. A total of 605 Nellore animals, raised by CFM Agro-pecuária Ltda, were used in this study and slaughtered with 24 months in average. After DNA blood samples extraction, by desproteinization in presence of NaCl, the polymorphism (CAPN316, CAPN530, CAPN4751, CAPN4753 and UOGACAST1) identification and determination was realized by TaqManTM detection system using real time PCR. The meat tenderness analysis, at the 7, 14 and 21 days of maturation was realized with Longissimus dorsi meat samples, taken at the 12th and 13th rib interval and Warner Bratzler Peak Shear Force measurements were used. There were no significant effects of molecular markers in growth traits. There were significant effects, regarding to meat tenderness, for following polymorphisms: at 7, 14 and 21 days of maturation, for CAPN4751 marker; at 21 days of maturation, for CAPN4753, and finally, at 14 and 21 days of maturation, for UOGCAST1 marker. In respect to genotypic combination effects analysis for pairwise marker, the results were significant for CAPN4751/UOGCAST1 in three days of maturation. In combination effects for CAPN4753/UOGCAST1 markers, significant effects were also observed for meat tenderness at 14 and 21 days. Theses results suggest that marked selection assisted (MAS) can be used to improve meat quality in Nellore beef cattle.
Xu, Jin. "Synthesis of novel sulfonamide-based calpain inhibitors and their potential as anti-tumor agents". View the abstract Download the full-text PDF version, 2007. http://etd.utmem.edu/WORLD-ACCESS/Xu/2007-028-Xu.pdf.
Pełny tekst źródłaTitle from title page screen (viewed on July 28, 2008). Research advisor: Dr. Isaac O. Donkor, Ph.D. Document formatted into pages (xii, 80 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 65-80).