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

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.

• Authors: Won-Seok Choi, Eunhee Lee, Junghyun Lim, Young J Oh
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 371 Issue 1 Pg. 127-31 (Jun 20 2008) ISSN: 1090-2104 [Electronic] United States
• PMID: 18413141 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calb1 protein, mouse
• Calbindin 1
• Calbindins
• Caspase Inhibitors
• Protein Kinase Inhibitors
• S100 Calcium Binding Protein G
• Calpain
• Staurosporine
• Dopamine

Topics

• Animals
• Apoptosis (genetics)
• Calbindin 1
• Calbindins
• Calpain (antagonists & inhibitors)
• Caspase Inhibitors
• Cell Line
• Dopamine (metabolism)
• Mice
• Neurons (drug effects, enzymology)
• Protein Kinase Inhibitors (pharmacology)
• S100 Calcium Binding Protein G (genetics, physiology)
• Staurosporine (pharmacology)