Impaired apoptosis in lymphoblasts from Alzheimer’s disease patients: Cross-talk of Ca2+/calmodulin and ERK1/2 signaling pathways
2007; Springer Nature; Volume: 64; Issue: 11 Linguagem: Inglês
10.1007/s00018-007-7081-3
ISSN1420-9071
AutoresFernando Benito Bartolomé, Natividad de las Cuevas, Úrsula Muñoz, F Bermejo, Ángeles Martín‐Requero,
Tópico(s)Cell death mechanisms and regulation
ResumoWe 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.
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