{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/34533"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/34533","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Up-regulation of junctophilin-2 prevents ER stress and apoptosis in hypoxia/reoxygenation-stimulated H9c2 cells","abstract":"Ischemic heart disease is the leading cause of death, and reperfusion which can restore blood flow is the primary therapy. However, reperfusion can induce further damage to cardiomyocytes, a condition described as ischemia-reperfusion (I/R) injury. I/R is now recognized as a combination determining the final myocardial infarction size. Although the mechanisms underlying I/R-induced cardiac injury remain incompletely understood, emerging evidence suggests that intracellular Ca2+ mishandling during I/R plays a key role in cell death. Junctophilin-2 (JPH2) is a junctional membrane-binding structural protein. It mechanically maintains the fixed distance between the T-tubule and the sarcoplasmic reticulum (SR), thus allowing the proper Ca2+-induced Ca2+ release for stable excitation-contraction coupling. Down-regulation of JPH2 has been observed in diseased hearts and is related to cardiac dysfunction and T-tubule remodeling. In this study, we show that the protein levels of JPH2 are down-regulated in cardiomyocytes following hypoxia/re-oxygenation (H/R), a condition simulating I/R. Up-regulation of JPH2 protects cardiomyocytes against H/R-induced apoptotic cell death. Furthermore, we reveal that up-regulation of JPH2 reduces ryanodine receptor-2 (RyR2)-mediated SR Ca2+ leak and inhibits calcium-dependent calpain activation in H/R-stimulated cardiomyocytes. Lastly, up-regulation of JPH2 prevents endoplasmic reticulum stress in response to H/R. In summary, we demonstrate for the first time that JPH2 prevents H/R-induced apoptosis by blocking Ca2+ leakage via RyR2 in cardiomyocytes. Thus, up-regulating JPH2 may represent a new therapeutic strategy to treat ischemic heart disease.","abstract_html":"Ischemic heart disease is the leading cause of death, and reperfusion which can restore blood flow is the primary therapy. However, reperfusion can induce further damage to cardiomyocytes, a condition described as ischemia-reperfusion (I/R) injury. I/R is now recognized as a combination determining the final myocardial infarction size. Although the mechanisms underlying I/R-induced cardiac injury remain incompletely understood, emerging evidence suggests that intracellular Ca2+ mishandling during I/R plays a key role in cell death. Junctophilin-2 (JPH2) is a junctional membrane-binding structural protein. It mechanically maintains the fixed distance between the T-tubule and the sarcoplasmic reticulum (SR), thus allowing the proper Ca2+-induced Ca2+ release for stable excitation-contraction coupling. Down-regulation of JPH2 has been observed in diseased hearts and is related to cardiac dysfunction and T-tubule remodeling. In this study, we show that the protein levels of JPH2 are down-regulated in cardiomyocytes following hypoxia/re-oxygenation (H/R), a condition simulating I/R. Up-regulation of JPH2 protects cardiomyocytes against H/R-induced apoptotic cell death. Furthermore, we reveal that up-regulation of JPH2 reduces ryanodine receptor-2 (RyR2)-mediated SR Ca2+ leak and inhibits calcium-dependent calpain activation in H/R-stimulated cardiomyocytes. Lastly, up-regulation of JPH2 prevents endoplasmic reticulum stress in response to H/R. In summary, we demonstrate for the first time that JPH2 prevents H/R-induced apoptosis by blocking Ca2+ leakage via RyR2 in cardiomyocytes. Thus, up-regulating JPH2 may represent a new therapeutic strategy to treat ischemic heart disease.","abstract_has_math":false,"creators":["Su, Zijun"],"institution":"The University of Western Ontario","degree_name":"M Sc","degree_level":null,"degree_discipline":"Pathology","degree_department":null,"school":null,"contributors":[],"advisors":["Dr.Tianqing Peng","Dr.Stephen Sims"],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-02-15","date_published":"2017-02-15","updated_at":"2026-07-27T21:55:54Z","subjects":["Cardiomyocytes","Junctophilin-2","RyR2","Calcium","Calpain","ER stress","JNK1/2","Apoptosis","hypoxia/re-oxygenation"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/34533","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Dr.Tianqing Peng","Dr.Stephen Sims"]},{"key":"dc:creator","label":"Author","values":["Su, Zijun"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T20:05:08Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T20:05:08Z"]},{"key":"dc:date.issued","label":"Date","values":["2017-02-15"]},{"key":"dc:publisher","label":"Institution","values":["The University of Western Ontario"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Pathology"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M Sc"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Cardiomyocytes","Junctophilin-2","RyR2","Calcium","Calpain","ER stress","JNK1/2","Apoptosis","hypoxia/re-oxygenation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_ca"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/34533"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["Ischemic heart disease is the leading cause of death, and reperfusion which can restore blood flow is the primary therapy. However, reperfusion can induce further damage to cardiomyocytes, a condition described as ischemia-reperfusion (I/R) injury. I/R is now recognized as a combination determining the final myocardial infarction size. Although the mechanisms underlying I/R-induced cardiac injury remain incompletely understood, emerging evidence suggests that intracellular Ca2+ mishandling during I/R plays a key role in cell death. Junctophilin-2 (JPH2) is a junctional membrane-binding structural protein. It mechanically maintains the fixed distance between the T-tubule and the sarcoplasmic reticulum (SR), thus allowing the proper Ca2+-induced Ca2+ release for stable excitation-contraction coupling. Down-regulation of JPH2 has been observed in diseased hearts and is related to cardiac dysfunction and T-tubule remodeling. In this study, we show that the protein levels of JPH2 are down-regulated in cardiomyocytes following hypoxia/re-oxygenation (H/R), a condition simulating I/R. Up-regulation of JPH2 protects cardiomyocytes against H/R-induced apoptotic cell death. Furthermore, we reveal that up-regulation of JPH2 reduces ryanodine receptor-2 (RyR2)-mediated SR Ca2+ leak and inhibits calcium-dependent calpain activation in H/R-stimulated cardiomyocytes. Lastly, up-regulation of JPH2 prevents endoplasmic reticulum stress in response to H/R. In summary, we demonstrate for the first time that JPH2 prevents H/R-induced apoptosis by blocking Ca2+ leakage via RyR2 in cardiomyocytes. Thus, up-regulating JPH2 may represent a new therapeutic strategy to treat ischemic heart disease."]},{"key":"dc:title","label":"Title","values":["Up-regulation of junctophilin-2 prevents ER stress and apoptosis in hypoxia/reoxygenation-stimulated H9c2 cells"]}]}],"canonical_facts":{"dc:contributor.advisor":["Dr.Tianqing Peng","Dr.Stephen Sims"],"dc:creator":["Su, Zijun"],"dc:date.accessioned":["2025-07-10T20:05:08Z"],"dc:date.available":["2025-07-10T20:05:08Z"],"dc:date.issued":["2017-02-15"],"dc:description":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."],"dc:description.abstract":["Ischemic heart disease is the leading cause of death, and reperfusion which can restore blood flow is the primary therapy. However, reperfusion can induce further damage to cardiomyocytes, a condition described as ischemia-reperfusion (I/R) injury. I/R is now recognized as a combination determining the final myocardial infarction size. Although the mechanisms underlying I/R-induced cardiac injury remain incompletely understood, emerging evidence suggests that intracellular Ca2+ mishandling during I/R plays a key role in cell death. Junctophilin-2 (JPH2) is a junctional membrane-binding structural protein. It mechanically maintains the fixed distance between the T-tubule and the sarcoplasmic reticulum (SR), thus allowing the proper Ca2+-induced Ca2+ release for stable excitation-contraction coupling. Down-regulation of JPH2 has been observed in diseased hearts and is related to cardiac dysfunction and T-tubule remodeling. In this study, we show that the protein levels of JPH2 are down-regulated in cardiomyocytes following hypoxia/re-oxygenation (H/R), a condition simulating I/R. Up-regulation of JPH2 protects cardiomyocytes against H/R-induced apoptotic cell death. Furthermore, we reveal that up-regulation of JPH2 reduces ryanodine receptor-2 (RyR2)-mediated SR Ca2+ leak and inhibits calcium-dependent calpain activation in H/R-stimulated cardiomyocytes. Lastly, up-regulation of JPH2 prevents endoplasmic reticulum stress in response to H/R. In summary, we demonstrate for the first time that JPH2 prevents H/R-induced apoptosis by blocking Ca2+ leakage via RyR2 in cardiomyocytes. Thus, up-regulating JPH2 may represent a new therapeutic strategy to treat ischemic heart disease."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/34533"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["Cardiomyocytes","Junctophilin-2","RyR2","Calcium","Calpain","ER stress","JNK1/2","Apoptosis","hypoxia/re-oxygenation"],"dc:title":["Up-regulation of junctophilin-2 prevents ER stress and apoptosis in hypoxia/reoxygenation-stimulated H9c2 cells"],"dc:type":["thesis"],"thesis:degree_discipline":["Pathology"],"thesis:degree_name":["M Sc"]},"updated_at":"2026-07-27T21:55:54Z"}