Apoptosis

, 13:1043

Resveratrol disrupts peroxynitrite-triggered mitochondrial apoptotic pathway: a role for Bcl-2

  • Paula M. Brito
  • Núria F. Simões
  • Leonor M. Almeida
  • Teresa C. P. Dinis
Original Paper

DOI: 10.1007/s10495-008-0235-4

Cite this article as:
Brito, P.M., Simões, N.F., Almeida, L.M. et al. Apoptosis (2008) 13: 1043. doi:10.1007/s10495-008-0235-4

Abstract

Resveratrol (3,4′,5-trihydroxystilbene) is a phytochemical believed to be partly responsible for the cardioprotective effects of red wine due to its numerous biological activities. Here, we studied biochemical pathways underlying peroxynitrite-mediated apoptosis in endothelial cells and potential mechanisms responsible for resveratrol cytoprotective action. Peroxynitrite triggered endothelial cell apoptosis through caspases-8, -9 and -3 activation implying both mitochondrial and death receptor apoptotic pathways. Resveratrol was able to prevent peroxynitrite-induced caspases-3 and -9 activation, but not caspase-8 activation. Additionally, peroxynitrite increased intracellular levels of Bax without affecting those of Bcl-2, increasing consequently the Bax/Bcl-2 ratio. This ratio decreased when cells where pre-incubated with 10 and 50 μM resveratrol, mainly due to resveratrol ability per se to increase Bcl-2 intracellular levels without affecting Bax intracellular levels. These results propose an additional mechanism whereby resveratrol may exert its cardioprotective effects and suggest a key role for Bcl-2 in the resveratrol anti-apoptotic action, especially in disrupting peroxynitrite-triggered mitochondrial pathway.

Keywords

ResveratrolPeroxynitriteBcl-2Cardioprotective effect

Abbreviations

NOS

Nitric oxide synthase

PARP-1

Poly(ADP-ribose) polymerase-1

BAEC

Bovine aortic endothelial cells

TMRM

Tetramethylrhodamine methyl ester

MOM

Mitochondrial outer membrane

PTP

Permeability transition pore

MPT

Mitochondrial permeability transition

GSH

Glutathione

ANT

Mitochondrial inner membrane protein adenine nucleotide translocase

CREB

cAMP response element-binding protein

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Paula M. Brito
    • 1
  • Núria F. Simões
    • 1
  • Leonor M. Almeida
    • 1
  • Teresa C. P. Dinis
    • 1
  1. 1.Laboratory of Biochemistry, Faculty of Pharmacy, Center of Neurosciences and Cell BiologyUniversity of CoimbraCoimbraPortugal