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

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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.

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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

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Acknowledgments

This work was supported by FCT (POCI/AGR/59919/2004). Paula Brito is a recipient of the grant SFRH/BD/7986/2001.

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Correspondence to Teresa C. P. Dinis.

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Brito, P.M., Simões, N.F., Almeida, L.M. et al. Resveratrol disrupts peroxynitrite-triggered mitochondrial apoptotic pathway: a role for Bcl-2. Apoptosis 13, 1043–1053 (2008). https://doi.org/10.1007/s10495-008-0235-4

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