p28GANK knockdown-derived reactive oxygen species induces apoptosis through mitochondrial dysfunction mediated by p38 in hepG2 cells

  • Authors: Xuefeng Wang, Honghai Li, Yao Chen, Jing Fu, Yibin Ren, Liwei Dong, Shanhua Tang, Shuqin Liu, Mengchao Wu, Hongyang Wang
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  • Published online on: Wednesday, October 1, 2008
  • Pages: 743-750
  • DOI: 10.3892/ijo_00000060

Abstract

Oncoprotein p28GANK knockdown by RNA interference (RNAi) can induce hepatoma cells apoptosis. However, the mechanisms have not been well defined yet. In the present study the p28GANK knockdown-induced apoptosis in HepG2 cells was prevented by caspase-9 inhibitor (Z-LEHD-FMK). During the knockdown of p28GANK, mitochondrial translocation of Bax, loss of mitochondrial transmembrane potential (ΔΨm) and release of cytochrome c were observed. In this study, the activation of p38 was found to be critical for the p28GANK knockdown-induced apoptosis, as suggested by the finding that pharmacological inhibition of p38 with SB203580 suppressed the redistribution of Bax, the loss of ΔΨm and the apoptosis. Moreover, generation of reactive oxygen species (ROS) contributed to the cell death because N-acetyl-L-cystenine (NAC), a ROS scavenger, suppressed the phosphorylation of p38 and the apoptosis. Our studies established the signaling pathway of p28GANK knockdown-induced apoptosis in HepG2 cells, namely, mitochondrial dysfunction mediated by p38 downstream of intracellular ROS generation.
Journal Cover

October 2008
Volume 33 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Wang, X., Li, H., Chen, Y., Fu, J., Ren, Y., Dong, L., Tang, S., Liu, S., Wu, M., & Wang, H. (2008). p28GANK knockdown-derived reactive oxygen species induces apoptosis through mitochondrial dysfunction mediated by p38 in hepG2 cells. International Journal of Oncology, 33(4), 743-750.
MLA
Wang, Li, Chen, Fu, Ren, Dong, Tang, Liu, Wu, and Hongyang Wang. "p28GANK knockdown-derived reactive oxygen species induces apoptosis through mitochondrial dysfunction mediated by p38 in hepG2 cells." International Journal of Oncology International Journal of Oncology 33.4 (2008): 743-750.
Chicago
Wang, Li, Chen, Fu, Ren, Dong, Tang, Liu, Wu, and Hongyang Wang. "p28GANK knockdown-derived reactive oxygen species induces apoptosis through mitochondrial dysfunction mediated by p38 in hepG2 cells." International Journal of Oncology International Journal of Oncology 33 no. 4 (2008): 743-750.