Calbindin-D28K inhibits apoptosis in dopaminergic neurons by activation of the PI3-kinase-Akt signaling pathway.
Calbindin-D28k (CaBP) has a neuroprotective effect on dopaminergic (DA) neurons in several models of Parkinson's disease. We used the DA cell line MN9D to explore the mechanisms underlying CaBP-mediated protection against the neurotoxin 6-hydroxydopamine (6-OHDA) of DA neurons. In MN9D cells that were transfected with the expression vector pcDNA3-CB containing CaBP cDNA, the expression level of CaBP was significantly increased. After treating with 6-OHDA, a significant decrease in the apoptosis rate of the transfected MN9D cells was noted, as well as an obvious increase in the expression of phosphorylation of Akt (p-Akt); however, no significant change in the expression of total Akt or phospho-p100 (p-p100) occurred after this treatment. After treatment with wortmannin, an inhibitor of the PI3-kinase-Akt (PI-3K/Akt) signal pathway, an increase in the expression level of CaBP was observed, but there were no other obvious changes of the experimental index mentioned previously in the groups transfected with pcDNA3-CB. These studies suggest that CaBP has a significant role in protecting DA cells against the apoptosis induced by 6-OHDA--through PI-3K/Akt signaling pathway--where the non-canonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway might have no relevance.
Department of Neurobiology, Xuzhou Medical College, Tongshan Road 209#, Xuzhou 221002, China.
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Sun
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Li
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Gao
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Zhu
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Chen
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Zhu
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Yuan
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Gao
D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D064092:Calbindin 1; D064026:Calbindins; D002460:Cell Line; D002469:Cell Separation; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D051379:Mice; D016627:Oxidopamine / Q000633:toxicity; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014162:Transfection
D018663:Adrenergic Agents; C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D004791:Enzyme Inhibitors; D064030:S100 Calcium Binding Protein G; D016627:Oxidopamine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt