Molecular and Cellular Biochemistry

, Volume 302, Issue 1–2, pp 99–109 | Cite as

Resveratrol-induced mitochondrial dysfunction and apoptosis are associated with Ca2+ and mCICR-mediated MPT activation in HepG2 cells

  • Xiaodong Ma
  • Xuemei Tian
  • Xingxu Huang
  • Fang Yan
  • Dongfang Qiao
Article

Abstract

Resveratrol, a natural polyphenolic antioxidant, has been reported to possess the cancer chemopreventive potential in wide range by means of triggering tumor cells apoptosis through various pathways. It induced apoptosis through the activation of the mitochondrial pathway in some kinds of cells. In the present reports, we showed that resveratrol-induced HepG2 cell apoptosis and mitochondrial dysfunction was dependent on the induction of the mitochondrial permeability transition (MPT), because resveratrol caused the collapse of the mitochondrial membrane potential (ΔΨm) with the concomitant release of cytochrome c (Cyt.c). In addition, resveratrol induced a rapid and sustained elevation of intracellular [Ca2+], which compromised the mitochondrial ΔΨm and triggered the process of HepG2 cell apoptosis. In permeabilized HepG2 cells, we further demonstrated that the effect of the resveratrol was indeed synergistic with that of Ca2+ and Ca2+ is necessary for resveratrol-induced MPT opening. Calcium-induced calcium release from mitochondria (mCICR) played a key role in mitochondrial dysfunction and cell apoptosis: (1) mCICR inhibitor, ruthenium red (RR), prevent MPT opening and Cyt.c release; and (2) RR attenuated resveratrol-induced HepG2 cell apoptotic death. Furthermore, resveratrol promotes MPT opening by lowering Ca2+-threshold. These data suggest modifying mCICR and Ca2+ threshold to modulate MPT opening may be a potential target to control cell apoptosis induced by resveratrol.

Keywords

Resveratrol Apoptosis Ca2+ Cytochrome c Mitochondrial permeability transition mCICR 

Notes

Acknowledgments

The study was supported by the Grant No. 30300455 of China Natural Science Foundation. The authors express thanks for the assistance from associate professor Ande Ma and Lianbo Chen for the excellent FACS analysis.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Xiaodong Ma
    • 1
  • Xuemei Tian
    • 2
  • Xingxu Huang
    • 1
  • Fang Yan
    • 2
  • Dongfang Qiao
    • 1
  1. 1.Instrumental Analysis & Research CenterSouthern Medical UniversityGuangzhouChina
  2. 2.Department of Histology and EmbryologySouthern Medical UniversityGuangzhouChina

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