G protein subunit levels in fibroblasts from familial Alzheimer's disease patients: lower levels of high molecular weight Gs alpha isoform in patients with decreased beta-adrenergic receptor stimulated cAMP formation.
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 Gs alpha, Gi alpha, Gq alpha and Go alpha 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 APPK670N,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 APPK670N,M671L FAD fibroblasts. Immunoreactivity for Go alpha 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 Go alpha are not associated with the G protein-coupled signal transduction disturbances described previously for some of these FAD fibroblasts.
Shanahan
C
C
Department of Biochemistry, University College, Lee Maltings, Cork, Ireland.
Gibson
G E
GE
Cowburn
R F
RF
Johnston
J A
JA
Wiehager
B
B
Lannfelt
L
L
O'Neill
C
C
D000544:Alzheimer Disease / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis*; D005192:Family Health; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology; D019204:GTP-Binding Proteins / Q000032:analysis* / Q000737:chemistry*; D006801:Humans; D007536:Isomerism; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000166:cytology
D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D019204:GTP-Binding Proteins