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  3. The protective effect of hispidin against hydrogen peroxide-induced apoptosis in H9c2 cardiomyoblast cells through Akt/GSK-3β and ERK1/2 signaling pathway

The protective effect of hispidin against hydrogen peroxide-induced apoptosis in H9c2 cardiomyoblast cells through Akt/GSK-3β and ERK1/2 signaling pathway

  • Exp Cell Res. 2014 Oct 1;327(2):264-75. doi: 10.1016/j.yexcr.2014.07.037.
Dae-Eun Kim 1,  Bokyung Kim 2,  Hwa-Sup Shin 3,  Ho Jeong Kwon 4,  Eun-Seok Park 5
Affiliations

Affiliations

  • 1 Department of Biomaterials Science and Engineering, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; Department of Biomedical Laboratory Science, Kyungbok University, Sinbuk-myeon, Pochen, Gyeonggi 487-717, Republic of Korea.
  • 2 Department of Physiology, Institute of Functional Genomics, Konkuk University School of Medicine, Chungju, Chungbuk 380-701, Republic of Korea.
  • 3 Department of Biomedical Chemistry, Konkuk University, Chungju, Chungbuk 380-701, Republic of Korea.
  • 4 Department of Biomaterials Science and Engineering, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; Department of Internal Medicine, College of Medicine, Yonsei University, Seoul 120-752, Republic of Korea. Electronic address: kwonhj@yonsei.ac.kr.
  • 5 Department of Biomedical Laboratory Science, Kyungbok University, Sinbuk-myeon, Pochen, Gyeonggi 487-717, Republic of Korea. Electronic address: eunspark@kbu.ac.kr.
PMID: 25128810 DOI: 10.1016/j.yexcr.2014.07.037
Abstract

Hispidin, a phenolic compound from Phellinus linteus (a medicinal mushroom), has been shown to possess strong anti-oxidant, anti-cancer, anti-diabetic, and anti-dementia properties. However, the cardioprotective efficacy of hispidin has not yet been investigated. In the present study, we investigated the protective effect of hispidin against oxidative stress-induced Apoptosis in H9c2 cardiomyoblast cells and neonatal rat ventricular myocytes. While the treatment of H9c2 cardiomyoblast cells with hydrogen peroxide caused a loss of cell viability and an increase in the number of apoptotic cells, hispidin significantly protected the cells against hydrogen peroxide-induced cell death without any cytotoxicity as determined by XTT assay, LDH release assay, Hoechst 33342 assay, and Western blotting of Apoptosis proteins such as Caspase-3, Bax, and Bcl-2. Our data also shows that hispidin significantly scavenged intracellular ROS, and markedly enhanced the expression of antioxidant Enzymes such as heme oxygenase-1 and catalase, which was accompanied by the concomitant activation of Akt/GSK-3β and ERK1/2 phosphorylation in H9c2 cardiomyoblast cells. The effects of hispidin on Akt and ERK phosphorylation were abrogated by LY294002 (a PI3K/Akt Inhibitor) and U0126 (an ERK1/2 inhibitor). The effect of hispidin on GSK-3b activities was also blocked by LY294002. Furthermore, inhibiting the Akt/GSK-3β and ERK1/2 pathway by these inhibitors significantly reversed the hispidin-induced Bax and Bcl-2 expression, Apoptosis induction, and ROS production. These findings indicate that hispidin protects against Apoptosis in H9c2 cardiomyoblast cells exposed to hydrogen peroxide through reducing intracellular ROS production, regulating apoptosis-related proteins, and the activation of the Akt/GSK-3β and ERK1/2 signaling pathways.

Keywords

Hispidin; Myocardial apoptosis; Oxidative stress; PKC inhibitor.

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