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Brain Res. 2001 Jun 8;903(1-2):226-30.

Cholinergic- and stress-induced signaling activities in cells overexpressing wild-type and mutant presenilin-1.

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  • 1Department of Psychiatry and Behavioral Neurobiology, Sparks Center 1057, University of Alabama at Birmingham, 35294-0017, USA.


This study examined the effects of overexpression of presenilin-1 wild-type (PS1wt) or mutant L286V (PS1m) in human neuroblastoma SH-SY5Y cells on signal transduction systems. Oxotremorine-M-induced activation of AP-1 was 40--53% lower in PS1wt than control cells, and further impaired (63--76%) in PS1m cells. Heat shock (45 degrees C) activated Akt, increased heat shock factor-1 (HSF-1) DNA binding activity, and increased levels of heat shock protein 70, and these responses were not altered by overexpression of PS1wt or PS1m. H(2)O(2) also caused a time-dependent increase in HSF-1 DNA binding activity which was similar in all cell lines. Thus, overexpression of PS1wt reduced muscarinic receptor-mediated activation of AP-1, and PS1m overexpression caused greater inhibition, but stress-induced activation of Akt and HSF-1 was unaffected by either PS1wt or PS1m.

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