Cholinergic- and stress-induced signaling activities in cells overexpressing wild-type and mutant presenilin-1.
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.
De Sarno
P
P
Department of Psychiatry and Behavioral Neurobiology, Sparks Center 1057, University of Alabama at Birmingham, 35294-0017, USA.
Lesort
M
M
Bijur
G N
GN
Johnson
G V
GV
Jope
R S
RS
D000109:Acetylcholine / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology; D009447:Neuroblastoma; D018384:Oxidative Stress / Q000502:physiology*; D010095:Oxotremorine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053764:Presenilin-1; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D018721:Muscarinic Agonists; C508853:PSEN1 protein, human; D053764:Presenilin-1; D011976:Receptors, Muscarinic; D010095:Oxotremorine; C042743:oxotremorine M; D000109:Acetylcholine