Altered cell growth and induction of an interferon-responsive gene in fibroblast lines derived from patients with familial Alzheimer's disease.
Cell growth and response to interferon (IFN) have been used to assess alteration in properties of cultured skin fibroblasts from patients with familial Alzheimer's Disease (AD). A comparison of the proliferative characteristics between "low" (7-11) and "high" (18-21) passage diploid fibroblasts from control and AD individuals shows that AD cells become severely restricted in their proliferative potential earlier than matched controls as a result of "in vitro aging". In addition, while control cells grow adequately in a serum-free, chemically-defined media (Nutridoma) (90-95% compared to FBS-supplemented media), AD cells grow poorly in Nutridoma (45-53% compared to FBS-supplemented media). An interferon (IFN)-inducible enzyme, 2'5'-oligoadenylate (2-5A) synthetase, is significantly reduced in IFN-treated AD cells compared to age-matched control cells in two cell passage-dependent manner. These data suggest that an intrinsic property of AD cells is the progressive reduced ability to interact with normal biologic signals provided by proteins such as interferons which in turn may contribute to the pathogenesis of AD.
Perret
V
V
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595.
An
S J
SJ
Wu
J M
JM
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis* / Q000737:chemistry; D000328:Adult; D000375:Aging; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002455:Cell Division; D002460:Cell Line; D003470:Culture Media; D004790:Enzyme Induction; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D046911:Macromolecular Substances; D011994:Recombinant Proteins
D003470:Culture Media; D007370:Interferon Type I; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase