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Elatoside C protects against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes through the reduction of endoplasmic reticulum stress partially depending on STAT3 activation

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Abstract

Endoplasmic reticulum (ER) stress-induced apoptosis has been suggested to contribute to myocardial ischemia–reperfusion (I/R) injury. Elatoside C is one of the major triterpenoid compounds isolated from Aralia elata that is known to be cardioprotective. However, its effects on I/R injury to cardiac myocytes have not been clarified. This study aimed to investigate the possible protective effect of Elatoside C against hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocyte injury and its underlying mechanisms. H9c2 cardiomyocytes were subjected to H/R in the presence of Elatoside C. Our results showed that Elatoside C (25 μM) treatment provided significant protection against H/R-induced cell death, as evidenced by improved cell viability, maintained mitochondrial membrane potential, diminished mitochondrial ROS, and reduced apoptotic cardiomyocytes (P < 0.05). These changes were associated with the inhibition of ER stress-associated apoptosis markers (GRP78, CHOP, Caspase-12 and JNK), as well as the increased phosphorylation of STAT3 and an increased Bcl2/Bax ratio. Moreover, these effects of Elatoside C were prevented by the STAT3 inhibitor Stattic. Taken together, these results suggested that Elatoside C can alleviate H/R-induced cardiomyocyte apoptosis most likely by activating the STAT3 pathways and reducing ER stress-associated apoptosis.

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Acknowledgments

This study was supported by the National Natural Sciences Foundation of China (Grant No. 81173589), Natural Sciences Foundation of Beijing (Grant No. 7142108), the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20121106110033), and the Key Scientific and Technological Project of Jilin Province (Grant No. 11ZDGG006).

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Authors and Affiliations

  1. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing, 100193, People’s Republic of China

    Min Wang, Xiang-bao Meng, Ying-li Yu, Gui-bo Sun, Xu-dong Xu, Xiao-po Zhang & Xiao-bo Sun

  2. Wenzhou Medical College, Wenzhou, 325035, Zhejiang, People’s Republic of China

    Xi Dong

  3. Jilin Agricultural University, No.2888, Xincheng Street, Changchun, 130118, Jilin, People’s Republic of China

    Jing-xue Ye

  4. Academy of Chinese Medical Sciences of Jilin Province, Gongnongda road 1745, Changchun, 130021, Jilin, People’s Republic of China

    Hui-bo Xu

  5. Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing, 100193, People’s Republic of China

    Yi-fan Sun

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  1. Min Wang
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Correspondence to Gui-bo Sun or Xiao-bo Sun.

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Wang, M., Meng, Xb., Yu, Yl. et al. Elatoside C protects against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes through the reduction of endoplasmic reticulum stress partially depending on STAT3 activation. Apoptosis 19, 1727–1735 (2014). https://doi.org/10.1007/s10495-014-1039-3

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  • DOI: https://doi.org/10.1007/s10495-014-1039-3

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