Dexmedetomidine attenuates H2O2-induced neonatal rat cardiomyocytes apoptosis through mitochondria- and ER-medicated oxidative stress pathways

Liu,Xue‑Ru; Li,Tao; Cao,Lu; Yu,Yi‑Yan; Chen,Lin‑Lin; Fan,Xue‑Hui; Yang,Bin‑Bin; Tan,Xiao‑Qiu

doi:10.3892/mmr.2018.8751

May-2018 Volume 17 Issue 5

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May-2018 Volume 17 Issue 5

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Article Open Access

Dexmedetomidine attenuates H2O2-induced neonatal rat cardiomyocytes apoptosis through mitochondria- and ER-medicated oxidative stress pathways

Authors:
- Xue‑Ru Liu
- Tao Li
- Lu Cao
- Yi‑Yan Yu
- Lin‑Lin Chen
- Xue‑Hui Fan
- Bin‑Bin Yang
- Xiao‑Qiu Tan
View Affiliations / Copyright

Affiliations: Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Key Laboratory of Medical Electrophysiology, Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease/Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China

Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 7258-7264
|
Published online on: March 15, 2018

https://doi.org/10.3892/mmr.2018.8751
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Abstract

Dexmedetomidine (DEX), an α2 adrenoceptor agonist, has sedative and analgesic properties and myocardial protective effects. However, the mechanism underlying the protective effects of DEX on the myocardium remain unclear. The present study aimed to determine whether DEX serves an important role on cardioprotection through the endoplasmic reticulum (ER)‑ and mitochondria‑mediated apoptosis signaling pathways. Neonatal rat cardiomyocytes (NRCMs) were cultured and divided four groups: i) Normal culture medium with 10% fetal bovine serum (control group); ii) H2O2 at 500 µM (H2O2 group); iii) DEX at 5 µM (DEX group); and iv) H2O2 plus DEX (H2O2 + DEX group). The levels of apoptosis and oxidative stress of NRCMs were investigated by ELISA, western blotting, flow cytometry and cell immunofluorescence. DEX significantly suppressed H2O2‑induced apoptosis, and increased activity of caspases 3, 8 and 9 of NRCMs. DEX inhibited mitochondria‑mediated oxidative stress and apoptosis, as evidenced by decreased levels of reactive oxygen species and lactic dehydrogenase, alleviated mitochondrial membrane potential depolarization, and increased Bcl‑2‑associated X protein/B‑cell lymphoma 2 ratio. In addition, DEX decreased the activity of caspase 12, and the expression levels of glucose‑regulated protein 78 kDa and serine/threonine‑protein kinase/endoribonuclease IRE1, three major signaling molecules involved in the ER stress‑mediated apoptosis pathway. Preventive treatment with DEX alleviates cardiomyocyte against H2O2‑induced oxidative stress injury through attenuating the mitochondria‑ and ER‑mediated apoptosis pathways.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Dexmedetomidine attenuates H2O2-induced neonatal rat cardiomyocytes apoptosis through mitochondria- and ER-medicated oxidative stress pathways

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