Melatonin-Induced Protective Effects on Cardiomyocytes Against Reperfusion Injury Partly Through Modulation of IP3R and SERCA2a Via Activation of ERK1
Resumo Background: Melatonin is a neuroendocrine hormone synthesized primarily by the pineal gland that is indicated to effectively prevent myocardial reperfusion injury. It is unclear whether melatonin protects cardiac function from reperfusion injury by modulating intracellular calcium homeostasi...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Sociedade Brasileira de Cardiologia (SBC)
|
| Series: | Arquivos Brasileiros de Cardiologia |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2018000100044&lng=en&tlng=en |
| _version_ | 1819237333327675392 |
|---|---|
| author | Shunying Hu Pingjun Zhu Hao Zhou Ying Zhang Yundai Chen |
| author_facet | Shunying Hu Pingjun Zhu Hao Zhou Ying Zhang Yundai Chen |
| author_sort | Shunying Hu |
| collection | DOAJ |
| description | Resumo Background: Melatonin is a neuroendocrine hormone synthesized primarily by the pineal gland that is indicated to effectively prevent myocardial reperfusion injury. It is unclear whether melatonin protects cardiac function from reperfusion injury by modulating intracellular calcium homeostasis. Objective: Demonstrate that melatonin protect against myocardial reperfusion injury through modulating IP3R and SERCA2a to maintain calcium homeostasis via activation of ERK1 in cardiomyocytes. Methods: In vitro experiments were performed using H9C2 cells undergoing simulative hypoxia/reoxygenation (H/R) induction. Expression level of ERK1, IP3R and SERCA2a were assessed by Western Blots. Cardiomyocytes apoptosis was detected by TUNEL. Phalloidin-staining was used to assess alteration of actin filament organization of cardiomyocytes. Fura-2 /AM was used to measure intracellular Ca2+ concentration. Performing in vivo experiments, myocardial expression of IP3R and SERCA2a were detected by immunofluorescence staining using myocardial ischemia/ reperfusion (I/R) model in rats. Results: In vitro results showed that melatonin induces ERK1 activation in cardiomyocytes against H/R which was inhibited by PD98059 (ERK1 inhibitor). The results showed melatonin inhibit apoptosis of cardiomyocytes and improve actin filament organization in cardiomyocytes against H/R, because both could be reversed by PD98059. Melatonin was showed to reduce calcium overload, further to inhibit IP3R expression and promote SERCA2a expression via ERK1 pathway in cardiomyocytes against H/R. Melatonin induced lower IP3R and higher SERCA2a expression in myocardium that were reversed by PD98059. Conclusion: melatonin-induced cardioprotection against reperfusion injury is at least partly through modulation of IP3R and SERCA2a to maintain intracellular calcium homeostasis via activation of ERK1. |
| first_indexed | 2024-12-23T13:18:40Z |
| format | Article |
| id | doaj.art-262d2db75b624122bf089df4b2c78340 |
| institution | Directory Open Access Journal |
| issn | 1678-4170 |
| language | English |
| last_indexed | 2024-12-23T13:18:40Z |
| publisher | Sociedade Brasileira de Cardiologia (SBC) |
| record_format | Article |
| series | Arquivos Brasileiros de Cardiologia |
| spelling | doaj.art-262d2db75b624122bf089df4b2c783402022-12-21T17:45:32ZengSociedade Brasileira de Cardiologia (SBC)Arquivos Brasileiros de Cardiologia1678-41701101445110.5935/abc.20180008S0066-782X2018000100044Melatonin-Induced Protective Effects on Cardiomyocytes Against Reperfusion Injury Partly Through Modulation of IP3R and SERCA2a Via Activation of ERK1Shunying HuPingjun ZhuHao ZhouYing ZhangYundai ChenResumo Background: Melatonin is a neuroendocrine hormone synthesized primarily by the pineal gland that is indicated to effectively prevent myocardial reperfusion injury. It is unclear whether melatonin protects cardiac function from reperfusion injury by modulating intracellular calcium homeostasis. Objective: Demonstrate that melatonin protect against myocardial reperfusion injury through modulating IP3R and SERCA2a to maintain calcium homeostasis via activation of ERK1 in cardiomyocytes. Methods: In vitro experiments were performed using H9C2 cells undergoing simulative hypoxia/reoxygenation (H/R) induction. Expression level of ERK1, IP3R and SERCA2a were assessed by Western Blots. Cardiomyocytes apoptosis was detected by TUNEL. Phalloidin-staining was used to assess alteration of actin filament organization of cardiomyocytes. Fura-2 /AM was used to measure intracellular Ca2+ concentration. Performing in vivo experiments, myocardial expression of IP3R and SERCA2a were detected by immunofluorescence staining using myocardial ischemia/ reperfusion (I/R) model in rats. Results: In vitro results showed that melatonin induces ERK1 activation in cardiomyocytes against H/R which was inhibited by PD98059 (ERK1 inhibitor). The results showed melatonin inhibit apoptosis of cardiomyocytes and improve actin filament organization in cardiomyocytes against H/R, because both could be reversed by PD98059. Melatonin was showed to reduce calcium overload, further to inhibit IP3R expression and promote SERCA2a expression via ERK1 pathway in cardiomyocytes against H/R. Melatonin induced lower IP3R and higher SERCA2a expression in myocardium that were reversed by PD98059. Conclusion: melatonin-induced cardioprotection against reperfusion injury is at least partly through modulation of IP3R and SERCA2a to maintain intracellular calcium homeostasis via activation of ERK1.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2018000100044&lng=en&tlng=enMelatoninaReperfusão MiocárdicaMiócitos CardíacosInfarto do MiocárdioInsuficiência Cardíaca |
| spellingShingle | Shunying Hu Pingjun Zhu Hao Zhou Ying Zhang Yundai Chen Melatonin-Induced Protective Effects on Cardiomyocytes Against Reperfusion Injury Partly Through Modulation of IP3R and SERCA2a Via Activation of ERK1 Arquivos Brasileiros de Cardiologia Melatonina Reperfusão Miocárdica Miócitos Cardíacos Infarto do Miocárdio Insuficiência Cardíaca |
| title | Melatonin-Induced Protective Effects on Cardiomyocytes Against Reperfusion Injury Partly Through Modulation of IP3R and SERCA2a Via Activation of ERK1 |
| title_full | Melatonin-Induced Protective Effects on Cardiomyocytes Against Reperfusion Injury Partly Through Modulation of IP3R and SERCA2a Via Activation of ERK1 |
| title_fullStr | Melatonin-Induced Protective Effects on Cardiomyocytes Against Reperfusion Injury Partly Through Modulation of IP3R and SERCA2a Via Activation of ERK1 |
| title_full_unstemmed | Melatonin-Induced Protective Effects on Cardiomyocytes Against Reperfusion Injury Partly Through Modulation of IP3R and SERCA2a Via Activation of ERK1 |
| title_short | Melatonin-Induced Protective Effects on Cardiomyocytes Against Reperfusion Injury Partly Through Modulation of IP3R and SERCA2a Via Activation of ERK1 |
| title_sort | melatonin induced protective effects on cardiomyocytes against reperfusion injury partly through modulation of ip3r and serca2a via activation of erk1 |
| topic | Melatonina Reperfusão Miocárdica Miócitos Cardíacos Infarto do Miocárdio Insuficiência Cardíaca |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2018000100044&lng=en&tlng=en |
| work_keys_str_mv | AT shunyinghu melatonininducedprotectiveeffectsoncardiomyocytesagainstreperfusioninjurypartlythroughmodulationofip3randserca2aviaactivationoferk1 AT pingjunzhu melatonininducedprotectiveeffectsoncardiomyocytesagainstreperfusioninjurypartlythroughmodulationofip3randserca2aviaactivationoferk1 AT haozhou melatonininducedprotectiveeffectsoncardiomyocytesagainstreperfusioninjurypartlythroughmodulationofip3randserca2aviaactivationoferk1 AT yingzhang melatonininducedprotectiveeffectsoncardiomyocytesagainstreperfusioninjurypartlythroughmodulationofip3randserca2aviaactivationoferk1 AT yundaichen melatonininducedprotectiveeffectsoncardiomyocytesagainstreperfusioninjurypartlythroughmodulationofip3randserca2aviaactivationoferk1 |