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Title: Hypochlorous acid induces apoptosis of cultured cortical neurons through activation of calpains and rupture of lysosomes
Authors: Yap, Y.W.
Whiteman, M.
Bay, B.H.
Li, Y. 
Sheu, F.-S. 
Qi, R.Z.
Tan, C.H.
Cheung, N.S.
Keywords: Alzheimer's disease
Hypochlorous acid
Oxidative stress
Issue Date: Sep-2006
Citation: Yap, Y.W., Whiteman, M., Bay, B.H., Li, Y., Sheu, F.-S., Qi, R.Z., Tan, C.H., Cheung, N.S. (2006-09). Hypochlorous acid induces apoptosis of cultured cortical neurons through activation of calpains and rupture of lysosomes. Journal of Neurochemistry 98 (5) : 1597-1609. ScholarBank@NUS Repository.
Abstract: 3-Chlorotyrosine, a bio-marker of hypochlorous acid (HOCl) in vivo, was reported to be substantially elevated in the Alzheimer's disease (AD) brains. Thus, HOCl might be implicated in the development of AD. However, its effect and mechanism on neuronal cell death have not been investigated. Here, we report for the first time that HOCl treatment induces an apoptotic-necrotic continuum of concentration-dependent cell death in cultured cortical neurons. Neurotoxicity caused by an intermediate concentration of HOCl (250 μm) exhibited several biochemical markers of apoptosis in the absence of caspase activation. However, the involvement of calpains was demonstrated by data showing that calpain inhibitors protect cortical neurons from apoptosis and the formation of 145/150 kDa α-fodrin fragments. Moreover, an increase in cytosolic Ca2+ concentration was associated with HOCl neurotoxicity and Ca2+ channel antagonists, and Ca2+ chelators prevented cleavage of α-fodrin and the induction of apoptosis. Finally, we found that calpain activation ruptured lysosomes. Stabilization of lysosomes by calpain inhibitors or imidazoline drugs, as well as inhibition of cathepsin protease activities, rescued cells from HOCl-induced neurotoxicity. Our results showed for the first time that HOCl induces apoptosis in cortical neurons, and that the cell death process involves calpain activation and rupture of lysosomes. © 2006 The Authors.
Source Title: Journal of Neurochemistry
ISSN: 00223042
Appears in Collections:Staff Publications

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