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Deficiency of presenilin‐1 increases calcium‐dependent vulnerability of neurons to oxidative stress in vitro
Author(s) -
Nakajima Mitsunari,
Miura Masami,
Aosaki Toshihiko,
Shirasawa Takuji
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00478.x
Subject(s) - oxidative stress , calcium , calcium channel blocker , p type calcium channel , calcium in biology , nifedipine , voltage dependent calcium channel , calcium channel , medicine , endocrinology , glutamate receptor , biology , neurotoxicity , chemistry , bapta , channel blocker , t type calcium channel , biochemistry , toxicity , receptor
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 H 2 O 2 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 H 2 O 2 ‐induced death, while an N‐type voltage‐dependent calcium channel blocker, ω‐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 H 2 O 2 . 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.