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

Won Seok Choi, Eunhee Lee, Junghyun Lim, Young Jun Oh

Research output: Contribution to journalArticle

34 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

Fingerprint

Calbindin 1
Dopamine Agents
Calpain
Caspases
Cell death
Staurosporine
Cell Death
Pharmaceutical Preparations
Calcium
Chemical activation
Sodium-Calcium Exchanger
Cells
1-Methyl-4-phenylpyridinium
Poly(ADP-ribose) Polymerases
Neuroprotective Agents
Buffers
Necrosis
Apoptosis
Cell Line
Processing

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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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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Calbindin-D28K prevents drug-induced dopaminergic neuronal death by inhibiting caspase and calpain activity. / Choi, Won Seok; Lee, Eunhee; Lim, Junghyun; Oh, Young Jun.

In: Biochemical and Biophysical Research Communications, Vol. 371, No. 1, 20.06.2008, p. 127-131.

Research output: Contribution to journalArticle

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