title: Caspase-3-mediated cleavage of PHF-1 tau during apoptosis irrespective of excitotoxicity and oxidative stress: an implication to Alzheimer's disease.
abstract: Excitotoxicity, oxidative stress, and apoptosis have been recognized as routes to neuronal death in various neurological diseases. We examined the possibility that PHF-1 tau, a substrate for various proteases, would be selectively cleaved depending upon routes of neuronal death. Cleavage form of PHF-1 tau was not observed in cortical cell cultures exposed to excitotoxins or oxidative stress that cause neuronal cell necrosis. PHF-1 tau was cleaved within 8 h following exposure of cortical cell cultures to apoptosis-inducing agents. This cleavage was blocked by inclusion of zDEVD-fmk, an inhibitor of caspase-3, and accompanied by activation of caspase-3. Levels and cleavage of PHF-1 tau were markedly increased in AD brain compared with control. Moreover, PHF-1 tau and active caspase-3 were colocalized mostly in tangle-bearing neurons. The current findings suggest that PHF-1 tau is cleaved by caspase-3 during apoptosis and neurodegenerative process in AD.
authors.affiliation: Department of Neuroscience, Ajou University School of Medicine, Suwon, Kyungkido, Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kang
authors.forename: Won Joo
authors.initials: WJ
authors.lastname: Yoon
authors.forename: Gyeong Joon
authors.initials: GJ
authors.lastname: Moon
authors.forename: Doo Yeon
authors.initials: DY
authors.lastname: Kim
authors.forename: Seonghyang
authors.initials: S
authors.lastname: Sohn
authors.forename: Hyuk Jae
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Byoung Joo
authors.initials: BJ
authors.lastname: Gwag
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000502:physiology*; D013379:Substrate Specificity; D016875:tau Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; C085349:PHF-1 monoclonal antibody; D016875:tau Proteins; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases