Molecular basis of 6-hydroxydopamine-induced caspase activations due to increases in oxidative stress in the mouse striatum.
To clarify the possible role of in the in vivo toxic effects of 6-hydroxydopamine (6-OHDA), especially caspase activations, we examined its effects on striatal lipid peroxidation (LPO) and caspase activations in 6-OHDA-lesioned mice. Both dopamine (DA) levels and DA turnover were significantly changed by the 6-OHDA i.c.v. injection compared with the pre-injection level in the striatum. In addition, the striatal glutathione (GSH) content fluctuated and was significantly decreased both at 3 and 14 days after 6-OHDA i.c.v. injection. Moreover, superoxide dismutase (SOD) activity at 7 days after 6-OHDA i.c.v. injection was transiently and significantly increased compared with the pre-injection level. The levels of thiobarbituric acid-reactive substances (TBA-RS) were significantly increased at 1, 3 and 14 days. 6-OHDA significantly increased the activities of all three caspases, except for the caspase-3 activity at 7 days throughout the experimental period compared with the pre-injection level. In conclusion, 6-OHDA-induced dopaminergic dysfunction is mainly due to caspase activations by increases in oxidative stress in the mouse striatum.
Tanaka
Ken-ichi
K
Department of Clinical Pharmacy, Shujitsu University School of Pharmacy, Okayama 703-8516, Japan. kntanaka@shujitsu.ac.jp
Ogawa
Norio
N
Asanuma
Masato
M
D018663:Adrenergic Agents / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D020169:Caspases / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D018663:Adrenergic Agents; D017392:Thiobarbituric Acid Reactive Substances; D016627:Oxidopamine; D013482:Superoxide Dismutase; D020169:Caspases; D004298:Dopamine