Chetsawang Jirapa, Mukda Sujira, Srimokra Rachneekorn, Govitrapong Piyarat, Chetsawang Banthit
Department of Anatomy, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
J Exp Neurosci. 2017 Jul 3;11:1179069517719237. doi: 10.1177/1179069517719237. eCollection 2017.
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.
细胞内钙水平过高会诱导钙蛋白酶激活，从而触发细胞死亡级联反应。多项证据表明，钙蛋白酶抑制剂钙蛋白酶抑制蛋白过表达具有神经保护作用。在本研究中，通过评估酪氨酸羟化酶磷酸化水平的降低来确定苯丙胺诱导的大鼠黑质变性。苯丙胺显著降低了钙蛋白酶抑制蛋白水平，但提高了钙蛋白酶水平。钙蛋白酶血影蛋白分解产物形成增加证明了钙蛋白酶活性的诱导。褪黑素预处理可减轻大鼠苯丙胺暴露的有害影响。此外，在人神经母细胞瘤SH-SY5Y细胞中研究了褪黑素对钙蛋白酶抑制蛋白表达的影响。褪黑素能够提高钙蛋白酶抑制蛋白水平，而这种作用可被褪黑素受体拮抗剂鲁辛朵阻断。这些结果证明了褪黑素的神经保护能力及其通过受体依赖性途径诱导钙蛋白酶抑制蛋白表达的作用。
