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

Abstract

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.

• Authors: P De Sarno, M Lesort, G N Bijur, G V Johnson, R S Jope
• Journal: Brain research (Brain Res) Vol. 903 Issue 1-2 Pg. 226-30 (Jun 08 2001) ISSN: 0006-8993 [Print] Netherlands
• PMID: 11382407 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Membrane Proteins
• Muscarinic Agonists
• PSEN1 protein, human
• Presenilin-1
• Receptors, Muscarinic
• Oxotremorine
• oxotremorine M
• Acetylcholine

Topics

• Acetylcholine (physiology)
• Gene Expression (physiology)
• Heat-Shock Response (physiology)
• Humans
• Membrane Proteins (genetics, metabolism)
• Muscarinic Agonists (pharmacology)
• Neuroblastoma
• Oxidative Stress (physiology)
• Oxotremorine (analogs & derivatives, pharmacology)
• Presenilin-1
• Receptors, Muscarinic (metabolism)
• Signal Transduction (drug effects, physiology)
• Tumor Cells, Cultured