Effect of 1,25-Dihydroxyvitamin D sub(3) on Cultured Mesencephalic Dopaminergic Neurons to the Combined Toxicity Caused by L-Buthionine Sulfoximine and 1-Methyl-4-Phenylpyridine

• Published in: Journal of neuroscience research 2000-11, Vol.62 (3), p.374-382
• Main Authors: Shinpo, K, Kikuchi, S, Sasaki, H, Moriwaka, F, Tashiro, K
• Format: Article
• Language: English
• Subjects: L-Buthionine sulfoximine
• ISSN: 0360-4012

A decrease in intracellular glutathione content may be related to the primary event in Parkinson's disease, so increasing the glutathione level may have a therapeutic benefit. The biologically active form of vitamin D, 1,25-dihydroxyvitamin D sub(3) [1,25-(OH) sub(2)D sub(3)] has been recently reported to enhance the intracellular glutathione concentration in the central nervous system. Exposing rat cultured mesencephalic neurons for 24 hr to a mixture of L-buthionine sulfoximine (BSO) and 1-methyl-4-phenylpyridium ions (MPP super(+)) resulted in a relatively selective damage to dopaminergic neurons. This damage has been accompanied by a reduction of intracellular glutathione levels. Low doses, i.e., 1-100 nM, of 1,25-(OH) sub(2)D sub(3) protect cultured dopaminergic neurons against this toxicity, although higher concentrations of this active form of vitamin D have been found to enhance the toxic effect. Generation of reactive oxygen species (ROS) by this toxicity has been attenuated in cultures being pretreated with low concentrations of 1,25-(OH) sub(2)D sub(3). Because the hormone increases the intracellular glutathione content in cultures, determining how this hormone suppresses ROS generation may involve the enhancement of the antioxidative system. These data suggest that low doses of 1,25-(OH) sub(2)D sub(3) are able to protect mesencephalic dopaminergic neurons against BSO/MPP super(+)-induced toxicity that causes a depletion in glutathione content.