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: Hyo Jung Kang, Won Joo Yoon, Gyeong Joon Moon, Doo Yeon Kim, Seonghyang Sohn, Hyuk Jae Kwon, Byoung Joo Gwag
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 18 Issue 3 Pg. 450-8 (Apr 2005) ISSN: 0969-9961 [Print] United States
• PMID: 15755671 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• PHF-1 monoclonal antibody
• tau Proteins
• CASP3 protein, human
• Casp3 protein, mouse
• Caspase 3
• Caspases

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (metabolism, pathology)
• Animals
• Antibodies, Monoclonal (metabolism)
• Apoptosis (physiology)
• Caspase 3
• Caspases (metabolism)
• Cell Proliferation
• Cells, Cultured
• Cerebral Cortex (metabolism, pathology)
• Humans
• Male
• Mice
• Mice, Inbred ICR
• Oxidative Stress (physiology)
• Substrate Specificity
• tau Proteins (immunology, metabolism)