Protective role of the deSUMOylating enzyme SENP3 in myocardial ischemia-reperfusion injury
Interruption of blood supply to the heart is a leading cause of death and disability. However, the molecular events that occur during heart ischemia, and how these changes prime consequent cell death upon reperfusion, are poorly understood. Protein SUMOylation is a post-translational modification th...
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| description | Interruption of blood supply to the heart is a leading cause of death and disability. However, the molecular events that occur during heart ischemia, and how these changes prime consequent cell death upon reperfusion, are poorly understood. Protein SUMOylation is a post-translational modification that has been strongly implicated in the protection of cells against a variety of stressors, including ischemia-reperfusion. In particular, the SUMO2/3-specific protease SENP3 has emerged as an important determinant of cell survival after ischemic infarct. Here, we used the Langendorff perfusion model to examine changes in the levels and localisation of SUMOylated target proteins and SENP3 in whole heart. We observed a 50% loss of SENP3 from the cytosolic fraction of hearts after preconditioning, a 90% loss after ischemia and an 80% loss after ischemia-reperfusion. To examine these effects further, we performed ischemia and ischemia-reperfusion experiments in the cardiomyocyte H9C2 cell line. Similar to whole hearts, ischemia induced a decrease in cytosolic SENP3. Furthermore, shRNA-mediated knockdown of SENP3 led to an increase in the rate of cell death upon reperfusion. Together, our results indicate that cardiac ischemia dramatically alter levels of SENP3 and suggest that this may a mechanism to promote cell survival after ischemia-reperfusion in heart. |
| doi_str_mv | 10.1371/journal.pone.0213331 |
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However, the molecular events that occur during heart ischemia, and how these changes prime consequent cell death upon reperfusion, are poorly understood. Protein SUMOylation is a post-translational modification that has been strongly implicated in the protection of cells against a variety of stressors, including ischemia-reperfusion. In particular, the SUMO2/3-specific protease SENP3 has emerged as an important determinant of cell survival after ischemic infarct. Here, we used the Langendorff perfusion model to examine changes in the levels and localisation of SUMOylated target proteins and SENP3 in whole heart. We observed a 50% loss of SENP3 from the cytosolic fraction of hearts after preconditioning, a 90% loss after ischemia and an 80% loss after ischemia-reperfusion. To examine these effects further, we performed ischemia and ischemia-reperfusion experiments in the cardiomyocyte H9C2 cell line. Similar to whole hearts, ischemia induced a decrease in cytosolic SENP3. Furthermore, shRNA-mediated knockdown of SENP3 led to an increase in the rate of cell death upon reperfusion. Together, our results indicate that cardiac ischemia dramatically alter levels of SENP3 and suggest that this may a mechanism to promote cell survival after ischemia-reperfusion in heart.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0213331</identifier><identifier>PMID: 30973885</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Apoptosis ; Biochemistry ; Biology and Life Sciences ; Cardiac function ; Cardiomyocytes ; Care and treatment ; Cell death ; Cell Death - genetics ; Cell Survival ; Diagnosis ; Endopeptidases - genetics ; Enzymes ; Gene Knockout Techniques ; Heart ; Heart attack ; Humans ; Ischemia ; Ischemic Preconditioning, Myocardial - methods ; Medicine and Health Sciences ; Mortality ; Myocardial ischemia ; Myocardial Ischemia - genetics ; Myocardial Ischemia - pathology ; Myocardial Reperfusion Injury - genetics ; Myocardial Reperfusion Injury - pathology ; Myocardium - metabolism ; Myocardium - pathology ; Myocytes, Cardiac - metabolism ; Oxidative Stress - genetics ; Perfusion ; Post-translation ; Post-translational modifications ; Preconditioning ; Proteases ; Proteins ; Rats ; Reperfusion ; Reperfusion injury ; RNA, Small Interfering - genetics ; Rodents ; Small Ubiquitin-Related Modifier Proteins - genetics ; SUMO protein ; Sumoylation - genetics ; Survival</subject><ispartof>PloS one, 2019-04, Vol.14 (4), p.e0213331-e0213331</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Rawlings et al. 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Together, our results indicate that cardiac ischemia dramatically alter levels of SENP3 and suggest that this may a mechanism to promote cell survival after ischemia-reperfusion in heart.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biology and Life Sciences</subject><subject>Cardiac function</subject><subject>Cardiomyocytes</subject><subject>Care and treatment</subject><subject>Cell death</subject><subject>Cell Death - genetics</subject><subject>Cell Survival</subject><subject>Diagnosis</subject><subject>Endopeptidases - genetics</subject><subject>Enzymes</subject><subject>Gene Knockout Techniques</subject><subject>Heart</subject><subject>Heart attack</subject><subject>Humans</subject><subject>Ischemia</subject><subject>Ischemic Preconditioning, Myocardial - methods</subject><subject>Medicine and Health Sciences</subject><subject>Mortality</subject><subject>Myocardial ischemia</subject><subject>Myocardial Ischemia - genetics</subject><subject>Myocardial Ischemia - 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However, the molecular events that occur during heart ischemia, and how these changes prime consequent cell death upon reperfusion, are poorly understood. Protein SUMOylation is a post-translational modification that has been strongly implicated in the protection of cells against a variety of stressors, including ischemia-reperfusion. In particular, the SUMO2/3-specific protease SENP3 has emerged as an important determinant of cell survival after ischemic infarct. Here, we used the Langendorff perfusion model to examine changes in the levels and localisation of SUMOylated target proteins and SENP3 in whole heart. We observed a 50% loss of SENP3 from the cytosolic fraction of hearts after preconditioning, a 90% loss after ischemia and an 80% loss after ischemia-reperfusion. To examine these effects further, we performed ischemia and ischemia-reperfusion experiments in the cardiomyocyte H9C2 cell line. Similar to whole hearts, ischemia induced a decrease in cytosolic SENP3. 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| subjects | Animals Apoptosis Biochemistry Biology and Life Sciences Cardiac function Cardiomyocytes Care and treatment Cell death Cell Death - genetics Cell Survival Diagnosis Endopeptidases - genetics Enzymes Gene Knockout Techniques Heart Heart attack Humans Ischemia Ischemic Preconditioning, Myocardial - methods Medicine and Health Sciences Mortality Myocardial ischemia Myocardial Ischemia - genetics Myocardial Ischemia - pathology Myocardial Reperfusion Injury - genetics Myocardial Reperfusion Injury - pathology Myocardium - metabolism Myocardium - pathology Myocytes, Cardiac - metabolism Oxidative Stress - genetics Perfusion Post-translation Post-translational modifications Preconditioning Proteases Proteins Rats Reperfusion Reperfusion injury RNA, Small Interfering - genetics Rodents Small Ubiquitin-Related Modifier Proteins - genetics SUMO protein Sumoylation - genetics Survival |
| title | Protective role of the deSUMOylating enzyme SENP3 in myocardial ischemia-reperfusion injury |
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