Previous work indicated that changes in Ca2+/calmodulin (CaM) signaling pathway are involved in the control
of proliferation and survival of immortalized lymphocytes from Alzheimer’s disease (AD) patients. We examined the
regulation of cellular CaM levels in AD lymphoblasts. An elevated CaM content in AD cells was found when compared
with control cells from age-matched individuals. We did not find significant differences in the expression of the three
genes that encode CaM: CALM1, 2, 3, by real time RT-PCR. However, we observed that the half-life of CaM was higher
in lymphoblasts from AD than in control cells, suggesting that degradation of CaM is impaired in AD lymphoblasts. The
rate of CaM degradation was found to be dependent on cellular Ca2+ and ROS levels. CaM degradation occurs mainly via
the ubiquitin-proteasome system. Increased levels of CaM were associated with overactivation of PI3K/Akt and CaMKII.
Our results suggest that increased levels of CaM synergize with serum to overactivate PI3K/Akt in AD cells by direct
binding of CaM to the regulatory α-subunit (p85) of PI3K. The systemic failure of CaM degradation, and thus of
Ca2+/CaM-dependent signaling pathways, may be important in the etiopathogenesis of AD.
Keywords: Alzheimer’s disease, Ca2+/Calmodulin, CaMKII, lymphocytes, PI3K/Akt, ROS
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