Differential regulation of adenylyl cyclase in fibroblasts from sporadic and familial Alzheimer's disease cases with PS1 and APP mutations.
beta-Adrenoceptor- and forskolin-stimulated adenylyl cyclase activities were determined in primary skin fibroblasts established from patients with sporadic Alzheimer's disease (AD) and from individuals with familial APP KM670/671NL, PS1 M146V and PS1 H163Y mutations. Our data showed a significantly decreased beta-adrenoceptor-stimulated adenylyl cyclase activity in fibroblasts from sporadic AD compared with age-matched controls (p < 0.001, Student's unpaired t-test). In contrast, both beta-adrenoceptor- and forskolin-stimulated adenylyl cyclase activities were significantly increased in fibroblasts bearing PS1 M146V and PS1 H163Y mutations compared with controls (p < 0.01 and p < 0.05, respectively). No differences were seen between cell lines with and without the Swedish APP KM670/671NL double mutation. We suggest that various gene mutations associated with AD have different consequences for the regulation of adenylyl cyclase signal transduction in this disorder.
Vestling
M
M
Division of Geriatric Medicine, Karolinska Institute, Novum, Huddinge, Sweden.
Adem
A
A
Racchi
M
M
Gibson
G E
GE
Lannfelt
L
L
Cowburn
R F
RF
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D053764:Presenilin-1; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000166:cytology
D000318:Adrenergic beta-Agonists; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D005576:Colforsin; D000262:Adenylyl Cyclases; D007545:Isoproterenol