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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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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DOI: https://doi.org/10.1007/s10495-008-0235-4