, 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


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.


Resveratrol Peroxynitrite Bcl-2 Cardioprotective effect 



Nitric oxide synthase


Poly(ADP-ribose) polymerase-1


Bovine aortic endothelial cells


Tetramethylrhodamine methyl ester


Mitochondrial outer membrane


Permeability transition pore


Mitochondrial permeability transition




Mitochondrial inner membrane protein adenine nucleotide translocase


cAMP response element-binding protein


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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

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