3,4-Dihydroxyphenylacetic acid (DOPAC) modulates the toxicity induced by nitric oxide in PC-12 cells via mitochondrial dysfunctioning

Neurotoxicology
Carla NunesJoão Laranjinha

Abstract

It has been postulated that dihydroxyphenylacetic acid (DOPAC), a major dopamine metabolite, and nitric oxide (NO) induce mitochondrial dysfunction in a synergistic manner. We examined the combined effects of NO and DOPAC on PC-12 cells in terms of cell viability, nuclear morphology, mitochondrial parameters and cell death mechanisms. The apoptotic cell death induced by the NO-donor, S-nitroso-N-acetylpenicillamine (SNAP), was differently modulated by DOPAC as a function of DOPAC/cell ratios. Whereas below 200nmol/10(6) cells, DOPAC inhibited a typical apoptotic pathway induced by exposure the cells to the NO donor, above 200nmol DOPAC/10(6) cells, the cell death was not only enhanced but encompassed a distinct mechanism. Loading the cells with dopamine mimicked the effects of DOPAC. Specifically, the combination of DOPAC and NO induced an early mitochondrial membrane potential dissipation and ATP depletion followed by loss of cellular membrane integrity. Mitochondrial dysfunction was accompanied by the release of cytochrome c in both cases, NO individually and in combination with DOPAC, but caspase-3 and caspase-9 activation were only observed in the absence of DOPAC. DOPAC alone was ineffective. Thus, our results suggest a ro...Continue Reading

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Citations

Jun 5, 2010·Journal of Medicinal Food·Chang-Hoon LeeMyung Sook Oh
Sep 28, 2010·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·F GagnéM Fournier
Jun 29, 2011·Molecular and Cellular Neurosciences·Carla NunesJoão Laranjinha
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Jun 11, 2021·Journal of the Electrochemical Society·Harmain Rafi, Alexander G Zestos

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