Deficiency of presenilin-1 increases calcium-dependent vulnerability of neurons to oxidative stress in vitro |
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Authors: | Nakajima M Miura M Aosaki T Shirasawa T |
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Institution: | Department of Molecular Genetics, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. |
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Abstract: | We examined the function of presenilin-1 (PS1) on neuronal resistance to oxidative stress. CNS neurons cultured from PS1-deficient mice exhibited increased vulnerability to H2O2 treatment compared with those from wild-type mice. Antioxidants protected the cultured neurons against the oxidative stress. An intracellular calcium chelator, BAPTA AM, as well as an L-type voltage-dependent calcium channel blocker, nifedipine, rescued the neurons from H2O2-induced death, while an N-type voltage-dependent calcium channel blocker, omega-conotoxin, or calcium release blockers from ER stores, dantrolene and xestospongin C, failed to rescue them. Wild-type and PS1-deficient neurons showed comparable increases of cytoplasmic free calcium levels after exposure to H2O2. Taken together with the data that PS1-deficient neurons exhibited increased vulnerability to glutamate, these findings imply that PS1 confers resistance to oxidative stress on neurons in calcium-dependent manners. |
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Keywords: | Alzheimer's disease BAPTA AM glutamate hydrogen peroxide neuronal death nifedipine |
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