Premium
Effect of 1,25‐dihydroxyvitamin D 3 on cultured mesencephalic dopaminergic neurons to the combined toxicity caused by L‐buthionine sulfoximine and 1‐methyl‐4‐phenylpyridine
Author(s) -
Shinpo Kazuyoshi,
Kikuchi Seiji,
Sasaki Hidenao,
Moriwaka Fumio,
Tashiro Kunio
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/1097-4547(20001101)62:3<374::aid-jnr7>3.0.co;2-7
Subject(s) - glutathione , buthionine sulfoximine , toxicity , intracellular , dopaminergic , chemistry , reactive oxygen species , pharmacology , endocrinology , medicine , biochemistry , biology , dopamine , enzyme
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 3 [1,25‐(OH) 2 D 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 + ) 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) 2 D 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) 2 D 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) 2 D 3 are able to protect mesencephalic dopaminergic neurons against BSO/MPP + ‐induced toxicity that causes a depletion in glutathione content. J. Neurosci. Res. 62:374–382, 2000. © 2000 Wiley‐Liss, Inc.