Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling
Mei Yuan,1,2,* Xiao-Wen Meng,1,* Jiao Ma,1,* Hong Liu,3 Shao-Yong Song,1 Qing-Cai Chen,1 Hua-Yue Liu,1 Juan Zhang,1 Nan Song,1 Fu-Hai Ji,1 Ke Peng11Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, People’s Republic of China; 2Department...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-09-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/dexmedetomidine-protects-h9c2-cardiomyocytes-against-oxygen-glucose-de-peer-reviewed-article-DDDT |
| _version_ | 1819037280726155264 |
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| author | Yuan M Meng XW Ma J Liu H Song SY Chen QC Liu HY Zhang J Song N Ji FH Peng K |
| author_facet | Yuan M Meng XW Ma J Liu H Song SY Chen QC Liu HY Zhang J Song N Ji FH Peng K |
| author_sort | Yuan M |
| collection | DOAJ |
| description | Mei Yuan,1,2,* Xiao-Wen Meng,1,* Jiao Ma,1,* Hong Liu,3 Shao-Yong Song,1 Qing-Cai Chen,1 Hua-Yue Liu,1 Juan Zhang,1 Nan Song,1 Fu-Hai Ji,1 Ke Peng11Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, People’s Republic of China; 2Department of Anesthesiology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215008, People’s Republic of China; 3Department of Anesthesiology and Pain Medicine, University of California Davis Health System, Sacramento, CA 95817, USACorrespondence: Fu-Hai Ji; Ke PengDepartment of Anesthesiology, First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, People’s Republic of ChinaTel +86 5 126 778 0055; +86 5 126 778 0159Email jifuhaisuda@163.com; pengke0422@163.com*These authors contributed equally to this workPurpose: Intracellular calcium ([Ca2+,]i) overload is a major cause of cell injury during myocardial ischemia/reperfusion (I/R). Dexmedetomidine (DEX) has been shown to exert anti-inflammatory and organ protective effects. This study aimed to investigate whether pretreatment with DEX could protect H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation (OGD/R) injury through regulating the Ca2+, signaling.Methods: H9c2 cardiomyocytes were subjected to OGD for 12 h, followed by 3 h of reoxygenation. DEX was administered 1 h prior to OGD/R. Cell viability, lactate dehydrogenase (LDH) release, level of [Ca2+,]i, cell apoptosis, and the expression of 12.6-kd FK506-binding protein/ryanodine receptor 2 (FKBP12.6/RyR2) and caspase-3 were assessed.Results: Cells exposed to OGD/R had decreased cell viability, increased LDH release, elevated [Ca2+,]i level and apoptosis rate, down-regulated expression of FKBP12.6, and up-regulated expression of phosphorylated-Ser2814-RyR2 and cleaved caspase-3. Pretreatment with DEX significantly blocked the above-mentioned changes, alleviating the OGD/R-induced injury in H9c2 cells. Moreover, knockdown of FKBP12.6 by small interfering RNA abolished the protective effects of DEX.Conclusion: This study indicates that DEX pretreatment protects the cardiomyocytes against OGD/R-induced injury by inhibiting [Ca2+,]i overload and cell apoptosis via regulating the FKBP12.6/RyR2 signaling. DEX may be used for preventing cardiac I/R injury in the clinical settings.Keywords: dexmedetomidine, H9c2 cardiomyocytes, oxygen-glucose deprivation/reoxygenation, apoptosis, intracellular calcium overload, FKBP12.6/RyR2 |
| first_indexed | 2024-12-21T08:18:55Z |
| format | Article |
| id | doaj.art-6510c54773ee4a05becdc827b2a81ac5 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-21T08:18:55Z |
| publishDate | 2019-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-6510c54773ee4a05becdc827b2a81ac52022-12-21T19:10:29ZengDove Medical PressDrug Design, Development and Therapy1177-88812019-09-01Volume 133137314948307Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signalingYuan MMeng XWMa JLiu HSong SYChen QCLiu HYZhang JSong NJi FHPeng KMei Yuan,1,2,* Xiao-Wen Meng,1,* Jiao Ma,1,* Hong Liu,3 Shao-Yong Song,1 Qing-Cai Chen,1 Hua-Yue Liu,1 Juan Zhang,1 Nan Song,1 Fu-Hai Ji,1 Ke Peng11Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, People’s Republic of China; 2Department of Anesthesiology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215008, People’s Republic of China; 3Department of Anesthesiology and Pain Medicine, University of California Davis Health System, Sacramento, CA 95817, USACorrespondence: Fu-Hai Ji; Ke PengDepartment of Anesthesiology, First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, People’s Republic of ChinaTel +86 5 126 778 0055; +86 5 126 778 0159Email jifuhaisuda@163.com; pengke0422@163.com*These authors contributed equally to this workPurpose: Intracellular calcium ([Ca2+,]i) overload is a major cause of cell injury during myocardial ischemia/reperfusion (I/R). Dexmedetomidine (DEX) has been shown to exert anti-inflammatory and organ protective effects. This study aimed to investigate whether pretreatment with DEX could protect H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation (OGD/R) injury through regulating the Ca2+, signaling.Methods: H9c2 cardiomyocytes were subjected to OGD for 12 h, followed by 3 h of reoxygenation. DEX was administered 1 h prior to OGD/R. Cell viability, lactate dehydrogenase (LDH) release, level of [Ca2+,]i, cell apoptosis, and the expression of 12.6-kd FK506-binding protein/ryanodine receptor 2 (FKBP12.6/RyR2) and caspase-3 were assessed.Results: Cells exposed to OGD/R had decreased cell viability, increased LDH release, elevated [Ca2+,]i level and apoptosis rate, down-regulated expression of FKBP12.6, and up-regulated expression of phosphorylated-Ser2814-RyR2 and cleaved caspase-3. Pretreatment with DEX significantly blocked the above-mentioned changes, alleviating the OGD/R-induced injury in H9c2 cells. Moreover, knockdown of FKBP12.6 by small interfering RNA abolished the protective effects of DEX.Conclusion: This study indicates that DEX pretreatment protects the cardiomyocytes against OGD/R-induced injury by inhibiting [Ca2+,]i overload and cell apoptosis via regulating the FKBP12.6/RyR2 signaling. DEX may be used for preventing cardiac I/R injury in the clinical settings.Keywords: dexmedetomidine, H9c2 cardiomyocytes, oxygen-glucose deprivation/reoxygenation, apoptosis, intracellular calcium overload, FKBP12.6/RyR2https://www.dovepress.com/dexmedetomidine-protects-h9c2-cardiomyocytes-against-oxygen-glucose-de-peer-reviewed-article-DDDTdexmedetomidineH9c2 cardiomyocytesoxygen-glucose deprivation/reoxygenationapoptosisintracellular calcium overloadFKBP12.6/RyR2 |
| spellingShingle | Yuan M Meng XW Ma J Liu H Song SY Chen QC Liu HY Zhang J Song N Ji FH Peng K Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling Drug Design, Development and Therapy dexmedetomidine H9c2 cardiomyocytes oxygen-glucose deprivation/reoxygenation apoptosis intracellular calcium overload FKBP12.6/RyR2 |
| title | Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling |
| title_full | Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling |
| title_fullStr | Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling |
| title_full_unstemmed | Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling |
| title_short | Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling |
| title_sort | dexmedetomidine protects h9c2 cardiomyocytes against oxygen glucose deprivation reoxygenation induced intracellular calcium overload and apoptosis through regulating fkbp12 6 ryr2 signaling |
| topic | dexmedetomidine H9c2 cardiomyocytes oxygen-glucose deprivation/reoxygenation apoptosis intracellular calcium overload FKBP12.6/RyR2 |
| url | https://www.dovepress.com/dexmedetomidine-protects-h9c2-cardiomyocytes-against-oxygen-glucose-de-peer-reviewed-article-DDDT |
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