Imbalance of catecholamine biosynthesis has been implicated as a major cause of neuronal cell death under hypoxia condition and how neurons respond physiologically to the effect of hypoxia is still poorly understood. There is increasing evidence suggesting that endogenous catecholamine itself could be the specific high vulnerability of neurons. Thus, dopaminergic mouse MN9D cell is used as a model to investigate the effect of hypoxia chemically induced by cobalt chloride on catecholamine biosynthesis. It is proposed that hypoxia increases acidosis that may lead to the perturbation of catecholamine biosynthesis. It causes an oxidative stress; possibility from the inhibition of mitochondrial activity that results in neuronal cell death.<br/><br/>Here, we have shown that cobalt chloride increases acidosis, reactive oxygen species production, and cell death and sodium/hydrogen exchanger inhibitor amiloride has no effect on cobalt chloride in MN9D cell. On the other hand, antioxidant ascorbic acid in the presence of cobalt chloride decreases reactive oxygen species production and cell death. In addition, anion exchanger inhibitor 4,4'-Diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) and enzyme tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine significantly decrease the effects of cobalt chloride in MN9D cell. Therefore, these findings suggest that perturbation of catecholamine biosynthesis resulted from the modulation of intracellular pH and oxidative stress may be implicated for the neuronal cell death. While it is not clearly understood how hypoxia chemically induced by cobalt chloride may lead to neuronal cell death, a better understanding of the mechanism of neuronal cell death under hypoxia condition could potentially lead to the development of pharmacological agents for the protection of neuronal damage.<br/>

Effect of hypoxia chemically induced by cobalt chloride on catecholamine biosynthesis in dopaminergic MN9D cell

2019 Fall National Meeting

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