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Title

Enhanced proliferation of lymphoblasts from patients with Alzheimer dementia associated with calmodulin-dependent activation of the Na+/H+ exchanger

AuthorsUrcelay, Elena; Ibarreta, Dolores; Parrilla, Roberto L. ; Sánchez Ayuso, Matilde ; Martín-Requero, Ángeles
Issue Date2001
PublisherAcademic Press
CitationNeurobiology of Disease 8(2):289-298(2001)
AbstractWe have recently reported that lymphoblasts from late onset Alzheimer's disease (AD) patients show distinct intracellular pH homeostatic features than those obtained from age-matched healthy donors. Here we report that another distinct feature of AD lymphoblasts is their increased rate of proliferation in serum containing medium, suggesting a different responsiveness of AD cells to serum activators. The increased proliferation of AD cells was accompanied by intracellular alkalinization and was prevented by blockers of the plasma membrane Na+/H+ antiporter (NHE), indicating that the exchanger had to be activated to elicit the cellular responses. The activity of this exchanger can be controlled through several signaling pathways, but only the inhibition of calmodulin activity impeded the serum-induced intracellular alkalinization and enhanced proliferation of AD cells. In contrast, the inhibition of calmodulin did not alter the rate of proliferation of normal cells. Thus, it seems plausible to conclude that the enhanced proliferation of AD cells is the result of a surface receptor-mediated activation of the Ca2+-calmodulin signaling pathway. Our observations add further support in favor that AD may be considered a systemic disease which underlying etiopathogenic mechanism may be an altered responsiveness to cell activating agents. Thus, the use of lymphoblastoid cells from AD patients may be a useful model to investigate cell biochemical aspects of this disease. © 2001 Academic Press.
URIhttp://hdl.handle.net/10261/72393
DOI10.1006/nbdi.2000.0381
Identifiersdoi: 10.1006/nbdi.2000.0381
issn: 0969-9961
e-issn: 1095-953X
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