| 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
(Affiliation: Department of Biology and Protein Network Research Center, Yonsei University, 134 Shincheondong Seodaemoonku, College of Science, Seoul 120-749, Republic of Korea.)
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| Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 371
Issue 1
Pg. 127-31
(Jun 20 2008)
ISSN: 1090-2104 United States |
| PMID | 18413141
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Calcium-Binding Protein, Vitamin D-Dependent
- Protein Kinase Inhibitors
- calbindin
- Dopamine
- Staurosporine
- Calpain
- Caspases
|
| Topics |
- Animals
- Apoptosis
(genetics)
- Calcium-Binding Protein, Vitamin D-Dependent
(genetics, physiology)
- Calpain
(antagonists & inhibitors)
- Caspases
(antagonists & inhibitors)
- Cell Line
- Dopamine
(metabolism)
- Mice
- Neurons
(drug effects, enzymology)
- Protein Kinase Inhibitors
(pharmacology)
- Staurosporine
(pharmacology)
|
