Calbindin-D28K prevents drug-induced dopaminergic neuronal death by inhibiting caspase and calpain activity

Won Seok Choi, Eunhee Lee, Junghyun Lim, Young J. Oh

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)127-131
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume371
Issue number1
DOIs
Publication statusPublished - 2008 Jun 20

Bibliographical note

Funding Information:
The authors thank Dr. A. Heller for allowing us to use the MN9D cell line. This work was supported by the Ministry of Health and Welfare (A050874), the Ministry of Science and Technology through the Brain Research Center (Infra-2) and the Korean Research Foundation (2007-7-0287).

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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