Restoration of TEA-induced calcium responses in fibroblasts from Alzheimer's disease patients by a PKC activator

NEUROBIOLOGY OF DISEASE

卷:5

Article

Bhagavan, S ; Ibarreta, D ; Ma, DW ; Kozikowski, AP ; Etcheberrigaray, R

关键词: Alzheimer's disease;    protein kinase C;    calcium;    TEA;    fibroblast;   

DOI  :  10.1006/nbdi.1998.0195

来源: Elsevier

【 摘 要 】

Several alterations in fibroblasts of Alzheimer's disease (AD) patients have been described, including alterations in calcium regulation, protein kinase C (PKC), and potassium (K+) channels. Studies have also found reduced levels of the or isoform of PKC in brains and fibroblasts of AD patients. Since PKC is known to regulate ion channels, we studied K+ channel activity in fibroblasts from AD patients in the presence of (2S, 5S)-8-(1-decynyl)benzolactam (BL), a novel activator of PKC with improved selectivity for the alpha, beta, and gamma isoforms. We present evidence for restoration of normal K+ channel function, as measured by TEA-induced [Ca2+](i) elevations, due to activation of PKC by BL. Representative patch-clamp data further substantiate the effect of BL on restoration of 113pS K+ channel activity. Immunoblotting analyses using an alpha-isozyme-specific PKC antibody confirm that BL-treated fibroblasts of AD patients show increased PKC activation. The present study suggests that PKC activator-based restoration of K+ channels may offer another approach to the investigation of AD pathophysiology, which in turn could lead to the development of a useful model for AD therapeutics, (C) 1998 Academic Press.

【 授权许可】

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