G protein subunit levels in fibroblasts from familial Alzheimer's disease patients: lower levels of the high molecular weight Gs alpha isoform in patients with decreased beta-adrenergic receptor stimulated cAMP formation

NEUROSCIENCE LETTERS

卷:232

Article

Shanahan, C ; Gibson, GE ; Cowburn, RF ; Johnston, JA ; Wiehager, B ; Lannfelt, L ; ONeill, C

关键词: familial Alzheimer's disease;    G proteins;    signal transduction;    cultured skin fibroblasts;   

DOI  :  10.1016/S0304-3940(97)00572-7

来源: Elsevier

【 摘 要 】

Abnormalities in G protein linked signal transduction pathways have been detected in fibroblasts from individuals with familial and sporadic Alzheimer's disease. The present study used Gsa, Gi alpha, Gq alpha and Goa G protein subunit antisera, immunoblotting and densitometry to quantify levels of these proteins in control fibroblasts and in fibroblasts from individuals with familial Alzheimer's disease (FAD). The FAD fibroblasts were from individuals with the APP(K670N.M671L) mutation, different presenilin 1 (PS1) mutations and one fibroblast cell line from an individual with FAD of unknown genetic aetiology. Results revealed a significant reduction in the large Gs alpha subunit in fibroblasts with the PS1 mutations and in the fibroblast cell line of unknown genetic aetiology, when compared to control levels. This decrease was not apparent in the APP(K670N,M671L) FAD fibroblasts, Immunoreactivity for Goa was not detected in any of the fibroblast cell lines. No differences were observed in Gi alpha or Gq alpha levels when comparing any of the control and Alzheimer's disease fibroblast groups. We conclude that with the exception of decreased levels of the large Gs alpha subunit, gross alterations in the levels of the Gi alpha, Gq alpha and Goer are not associated with the G protein-coupled signal transduction disturbances described previously for some of these FAD fibroblasts. (C) 1997 Elsevier Science ireland Ltd.

【 授权许可】

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