Calpain activation in okadaic-acid-induced neurodegeneration.
Calpain activation has been implicated in the pathogenesis of Alzheimer's disease. Okadaic acid, a protein phosphatase-2A inhibitor, has been used in Alzheimer's disease research models to increase tau phosphorylation and induce neuronal death. We previously reported that okadaic acid induced predominant activation of caspase-3 in immature neurons, but less activation in mature neurons. We found here that, in okadaic-acid-treated mature neurons, levels of an inactive form of m-calpain decreased and levels of calpain-cleaved spectrin and synapsin-I fragments increased, suggestive of calpain activation. Pretreatment with calpain inhibitor decreased lactate dehydrogenase release by 20% and increased average dendritic branch length by 50% compared with neurons treated with okadaic acid alone. These findings suggest that calpain is activated during okadaic-acid-induced neurodegeneration and calpain inhibition can be protective against it.
Yoon
SeungYong
S
Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea.
Choi
JungEun
J
Huh
Jae-Wan
JW
Hwang
Onyou
O
Kim
DongHou
D
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002154:Calpain / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity*; D006023:Glycoproteins / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D019319:Okadaic Acid / Q000633:toxicity*; D051381:Rats
D004791:Enzyme Inhibitors; D006023:Glycoproteins; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; C039304:calpain inhibitors; D019319:Okadaic Acid; D007770:L-Lactate Dehydrogenase; D002154:Calpain; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases