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C2C12 근아세포에서 산자나무 유래 Isorhamnetin의 산화적 스트레스에 의한 Apoptosis 유발 억제 효과

Protective Effects of Isorhamnetin against Hydrogen Peroxide-Induced Apoptosis in C2C12 Murine Myoblasts

  • 최영현 (동의대학교 한의과대학 생화학교실 및 항노화연구소)
  • Choi, Yung Hyun (Department of Biochemistry, College of Korean Medicine and Anti-Aging Research Center, Dong-Eui University)
  • 투고 : 2015.09.19
  • 심사 : 2015.11.23
  • 발행 : 2015.12.30

초록

Objectives: It was investigated the cytoprotective efficacies of isorhamnetin, a flavonoid originally derived from Hippophae rhamnoides L., against oxidative stress-induced apoptosis in C2C12 myoblasts. Methods: The effects of isorhamnetin on cell growth, apoptosis and reactive oxygen species (ROS) generation were evaluated by trypan blue dye exclusion assay, 4',6-diamidino-2-phenylindole staining and flow cytometry. The levels of apoptosis-regulatory and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway-related proteins, and caspase activities (caspase-3 and -9) were determined by Western blot analysis and colorimetric assay, respectively. Results: Our results revealed that treatment with isorhamnetin prior to hydrogen peroxide ($H_2O_2$) exposure significantly increased the C2C12 cell viability and, indicating that the exposure of C2C12 cells to isorhamnetin conferred a protective effect against oxidative stress. Isorhamnetin also effectively attenuated $H_2O_2$-induced apoptosis and ROS generation, which was associated with the restoration of the upregulation of Bax and downregulation of Bcl-2 induced by $H_2O_2$. In addition, $H_2O_2$ enhanced the activation of caspase-9 and -3, and degradation of poly (ADP-ribose)-polymerase, a typical substrate protein of activated caspase-3; however, these events were almost totally reversed by pretreatment with isorhamnetin. Moreover, isorhamnetin increased the levels of heme oxygenase-1, a potent antioxidant enzyme, associated with the induction of Nrf2. Conclusions: Our data indicated that isorhamnetin may potentially serve as an agent for the treatment and prevention of muscle disorders caused by oxidative stress.

키워드

참고문헌

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