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Overexpression of α7 nicotinic acetylcholine receptor prevents G1‐arrest and DNA fragmentation in PC12 cells after hypoxia
Author(s) -
Utsugisawa Kimiaki,
Nagane Yuriko,
Obara Daiji,
Tohgi Hideo
Publication year - 2002
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.1471-4159.2002.00823.x
Subject(s) - dna fragmentation , nicotine , hypoxia (environmental) , transfection , nicotinic agonist , nicotinic acetylcholine receptor , microbiology and biotechnology , acetylcholine receptor , chemistry , fragmentation (computing) , cell culture , biology , receptor , apoptosis , programmed cell death , biochemistry , neuroscience , ecology , genetics , organic chemistry , oxygen
We investigated the neuroprotective function of α7 nicotinic acetylcholine receptor (α7nAChR) after transient hypoxia (12 h) and reoxygenation (0–72 h), comparing rat pheochromocytoma (PC12) cells overexpressing FLAG‐tagged α7nAChR (α7pCMV cells) and control PC12 cells (non‐transfected or transfected with vector only) in medium with and without nicotine. Plasma membrane degradation in the early phase after hypoxia was inhibited in PC12 cells with nicotine, and more profoundly in α7pCMV cells with nicotine. Inhibition of DNA fragmentation in the late phase after hypoxia was most remarkable in α7pCMV cells with nicotine, but, surprisingly, it was more remarkable in α7pCMV cells without nicotine than in PC12 cells with nicotine. G1‐arrest of the cell cycle, observed in control PC12 cells at 12 h after hypoxia, preceding DNA fragmentation, was not evident in α7pCMV cells, with or without nicotine. Furthermore, in α7pCMV cells with and without nicotine, the basal expression levels of total Akt were approximately 1.5‐fold higher, and the up‐regulation of Akt phosphorylated at Ser473 after hypoxia was strikingly enhanced, compared with control PC12 cells. These findings suggest that α7nAChR functions constitutively in PC12 cells, that its overexpression raises tolerance against G1‐arrest and DNA fragmentation after hypoxia, and that it can be considered a candidate target for treatment against hypoxia‐induced acute membrane degradation and delayed DNA fragmentation in neurons.