PMID: 8592119Feb 1, 1996Paper

L-DOPA up-regulates glutathione and protects mesencephalic cultures against oxidative stress

Journal of Neurochemistry
S K HanG Cohen

Abstract

Incubation with L-DOPA induced a rise in GSH level in cultures of fetal rat mesencephalon, mouse neuroblastoma (Neuro-2A), human neuroblastoma (SK-N-MC), pig kidney epithelial cells (LLC-PK1), and glia from newborn rat brain, but not C6 glioma cells or neuronal cultures (no glia) from the mesencephalon. The pure neuronal cultures were destroyed by incubation with L-DOPA; added ascorbic acid or superoxide dismutase protected the cells. Washout of L-DOPA after 48 h amplified the rise in GSH content in mixed cultures (neurons plus glia). Examination of structure-activity relationships for elevating GSH levels in responsive cell types revealed that autooxidizable compounds (alpha-methyl-DOPA, dopamine, apomorphine, catechol, and hydroquinone) behaved similarly to L-DOPA, whereas structural analogues that cannot undergo autooxidation (3-O-methyl-DOPA, tyrosine, 2,4-dihydroxyphenylalanine, and resorcinol) failed to elevate GSH levels. Therefore, up-regulation of GSH appears to be a response to a mild oxidative stress. When mixed mesencephalic cultures were exposed to a strong oxidant stress by incubation with tert-butyl hydroperoxide, a loss in viability was seen. Cultures pretreated with L-DOPA or hydroquinone were protected from lo...Continue Reading

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