Abstract
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
Current Alzheimer Research
Title:Altered Calmodulin Degradation and Signaling in Non-Neuronal Cells from Alzheimer’s Disease Patients
Volume: 9 Issue: 3
Author(s): Noemi Esteras, Ursula Munoz, Carolina Alquezar, Fernando Bartolome, Felix Bermejo-Pareja and Angeles Martin-Requero
Affiliation:
Keywords: Alzheimer’s disease, Ca2+/Calmodulin, CaMKII, lymphocytes, PI3K/Akt, ROS
Abstract: 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.
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Esteras Noemi, Munoz Ursula, Alquezar Carolina, Bartolome Fernando, Bermejo-Pareja Felix and Martin-Requero Angeles, Altered Calmodulin Degradation and Signaling in Non-Neuronal Cells from Alzheimer’s Disease Patients, Current Alzheimer Research 2012; 9 (3) . https://dx.doi.org/10.2174/156720512800107564
DOI https://dx.doi.org/10.2174/156720512800107564 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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