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  • Title: Calbindin-D28K prevents drug-induced dopaminergic neuronal death by inhibiting caspase and calpain activity.
    Author: Choi WS, Lee E, Lim J, Oh YJ.
    Journal: Biochem Biophys Res Commun; 2008 Jun 20; 371(1):127-31. PubMed ID: 18413141.
    Abstract:
    Calbindin-D28K protects against apoptotic and necrotic cell death; these effects have been attributed to its ability to buffer calcium. In this study, we investigated the mechanisms underlying the neuroprotective effects of calbindin-D28K in staurosporine (STS)-induced apoptosis and 1-methyl-4-phenylpyridinium (MPP(+))-induced necrosis. Treatment of the dopaminergic neuronal cell line MN9D with STS or MPP(+) induced cell death that was associated with increased levels of free intracellular calcium. However, only MPP(+)-induced death was inhibited by co-treatment of the cells with a calcium chelator or a sodium/calcium antiporter inhibitor. Overexpression of calbindin-D28K prevented MPP(+)-induced MN9D cell death, which occurs in the absence of any detectable caspase activation. These pro-survival effects of calbindin-D28K were associated with the inhibition of calcium-mediated calpain activation, as determined by processing of Bax. Overexpression of calbindin-D28K also blocked STS-induced MN9D death. However, this effect was accompanied by the inhibition of capase-3 cleavage, poly(ADP-ribose)polymerase cleavage, and caspase activity. These findings suggest that calbindin-D28K protects against both types of cell death by inhibiting caspase- or calcium-mediated death signaling pathway.
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