Homocysteine is toxic for dopaminergic neurons in primary mesencephalic culture.
Hyperhomocysteinemia associated with L-3,4-dihydroxyphenylalanine (L-dopa) treatment has been observed in patients with Parkinson's disease. We investigated the toxicity of homocysteine (Hcy) on E14-rat-primary mesencephalic culture. Exposure to 0-5 mM Hcy decreased number of tyrosine hydroxylase (TH)-positive dopaminergic neurons and microtubule associated protein 2 (MAP2)-positive neurons in a dose-dependent manner. TH-positive neurons had vulnerability to the insult of Hcy compared with the other MAP2-positive neurons. In dopaminergic neurons, 5 microM reserpine enhanced the Hcy toxicity, whereas 50 microM alpha-methyltyrosine attenuated the toxic effect, showing that the intracellular dopamine increased the cytotoxicity of Hcy. Hcy enhanced the toxicity of 1-methyl-4-phenylpyridinium (MPP+) for dopaminergic neurons. It was suggested that the Hcy toxicity was associated with the oxidative stress. Hcy is toxic for dopaminergic neurons, and hyperhomocysteinemia may modify the clinical course of Parkinson's disease.
Imamura
Keiko
K
Department of Neurology, Institute of Neurological Science, Tottori University, Faculty of Medicine, Yonago, Tottori, Japan. imamurakeiko@nifty.com
Takeshima
Takao
T
Nakaso
Kazuhiro
K
Nakashima
Kenji
K
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004622:Embryo, Mammalian; D005260:Female; D006710:Homocysteine / Q000633:toxicity*; D008636:Mesencephalon / Q000166:cytology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009498:Neurotoxins / Q000493:pharmacokinetics; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014150:Antipsychotic Agents; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D009498:Neurotoxins; D006710:Homocysteine; D012110:Reserpine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine