期刊
JOURNAL OF EXPERIMENTAL NEUROSCIENCE
卷 11, 期 -, 页码 -出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1179069517719237
关键词
Amphetamine; calpain; calpastatin; melatonin; rat brain; neuroprotection
资金
- Mahidol University
- Thailand Research Fund (TRF) under TRF Basic Research Grant [BRG5780003]
- TRF [DPG5780001, IRG5780009]
Excessive intracellular calcium levels induce calpain activation, thereby triggering the cell death cascade. Several lines of evidence have demonstrated the neuroprotective role of the overexpression of calpain inhibitor, calpastatin. In this study, amphetamine-induced degeneration in the substantia nigra of rats was determined by evaluating the decrease in the levels of tyrosine hydroxylase phosphorylation. Amphetamine significantly decreased calpastatin levels but increased calpain levels. An induction in calpain activity was demonstrated by an increase in the formation of calpain spectrin breakdown products. The deleterious effects of amphetamine exposure were diminished in rats by pretreatment with melatonin. In addition, the effect of melatonin on calpastatin expression was investigated in human neuroblastoma SH-SY5Y cells. Melatonin was able to increase the calpastatin levels, and this effect could be blocked by luzindole, a melatonin receptor antagonist. These results demonstrate the neuroprotective ability of melatonin and its role in inducing calpastatin expression via a receptor-dependent pathway.
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