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Title

Impaired apoptosis in lymphoblasts from Alzheimer´s disease patients: Cross-talk of Ca(2+)/calmodulin and ERK1/2 signaling pathways

AuthorsBartolomé Robledo, Fernando ; De las Cuevas, Natividad; Muñoz, Úrsula ; Bermejo-Pareja, Félix; Martín-Requero, Ángeles
KeywordsAlzheimer’s disease
lymphocytes
cell survival
Ca2+/calmodulin
ERKs
Issue DateJun-2007
PublisherSpringer
CitationCellular and Molecular Life Sciences, 64 (11) : 1437-1448 (2007)
AbstractWe have analyzed the intracellular signals that allow lymphoblasts from Alzheimer’s disease (AD) patients to escape from serum deprivation-induced apoptosis. The following observations suggested that modulation of ERK1/2 activity by Ca2+/calmodulin (CaM) is involved in preventing apoptosis: (i) ERK1/2 activity seems to support lethality in control cells, as PD98059, the inhibitor of the activating MEK prevented cell death; (ii) control cells show a persistent and higher stimulation of ERK1/2 than that of AD cells in the absence of serum; (iii) CaM antagonists have no effects on control cells, but sensitize AD cells to death induced by serum withdrawal and increased ERK1/2 phosphorylation, and (iv) no apoptotic effects of CaM antagonists were observed in AD cells treated with PD98059. These results suggest the existence of an activation threshold of the ERK1/2 pathway setting by Ca2+/CaM-dependent mechanisms, which appears to be the critical factor controlling cell survival or death decision under trophic factor withdrawal
Description12 páginas, 11 figuras -- PAGS nros. 1437-1448
Publisher version (URL)http://dx.doi.org/10.1007/s00018-007-7081-3
URIhttp://hdl.handle.net/10261/72387
DOI10.1007/s00018-007-7081-3
ISSN1420-682X
E-ISSN1420-9071
Appears in Collections:(CIB) Artículos
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