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Propofol attenuates H2O2-induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes

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Abstract

Previous studies have shown that propofol, an intravenous anesthetic commonly used in clinical practice, protects the myocardium from injury. Mitochondria- and endoplasmic reticulum (ER)-mediated oxidative stress and apoptosis are two important signaling pathways involved in myocardial injury and protection. The present study aimed to test the hypothesis that propofol could exert a cardio-protective effect via the above two pathways. Cultured neonatal rat cardiomyocytes were treated with culture medium (control group), H2O2 at 500 μM (H2O2 group), propofol at 50 μM (propofol group), and H2O2 plus propofol (H2O2 + propofol group), respectively. The oxidative stress, mitochondrial membrane potential (ΔΨm) and apoptosis of the cardiomyocytes were evaluated by a series of assays including ELISA, flow cytometry, immunofluorescence microscopy and Western blotting. Propofol significantly suppressed the H2O2-induced elevations in the activities of caspases 3, 8, 9 and 12, the ratio of Bax/Bcl-2, and cell apoptosis. Propofol also inhibited the H2O2-induced reactive oxygen species (ROS) generation, lactic dehydrogenase (LDH) release and mitochondrial transmembrane potential (ΔΨm) depolarization, and restored the H2O2-induced reductions of glutathione (GSH) and superoxide dismutase (SOD). In addition, propofol decreased the expressions of glucose-regulated protein 78 kDa (Grp78) and inositol-requiring enzyme 1α (IRE1α), two important signaling molecules in the ER-mediated apoptosis pathway. Propofol protects cardiomyocytes from H2O2-induced injury by inhibiting the mitochondria- and ER-mediated apoptosis signaling pathways.

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Acknowledgements

The research was supported by the National Natural Science Fundation of China (81670310), and Southwest Medical University Scientific Research Fund (2014QN-003). Authors would like to thank Prof. Ji-Min Cao from Chinese Academy of Medical Sciences and Prof. Xitong Dang from the University of California, San Diego for their critical reading of the manuscript.

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    Authors and Affiliations

    1. Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China

      Xue-Ru Liu, Lu Cao & Li Liu

    2. 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, China

      Tao Li, Lin-Lin Chen, Yi-Yan Yu, Wen-Jun Huang & Xiao-Qiu Tan

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    Xue-Ru Liu, Lu Cao and Tao Li have contributed equally to this work.

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    Liu, XR., Cao, L., Li, T. et al. Propofol attenuates H2O2-induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes. Apoptosis 22, 639–646 (2017). https://doi.org/10.1007/s10495-017-1349-3

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