Increased IFN-alpha-induced sensitivity but reduced reactivity of 2',5'-oligoadenylate synthetase (2,5AS) in trisomy 21 blood lymphocytes.
2,5AS is induced by interferon-alpha, -beta (IFN-alpha, -beta) and polymerizes adenosine triphosphate (ATP) into pppA (2'p5'A) oligomers, leading to inhibition of protein synthesis and virus growth. The gene coding for the IFN-alpha, -beta receptor is localized to chromosome 21. In trisomy 21 cells from patients with Down's syndrome a 50% increase in gene dosage is present for the genes on this chromosome. Corresponding increase of gene products has been shown for several of these genes, e.g. the IFN-alpha, -beta receptor molecules. Here, we show a direct proportionality between the number of IFN-alpha, -beta receptors and both the basal activity of 2,5AS and the sensitivity of this enzyme for IFN-alpha, -beta. The relative increase of 2,5AS activity (the reactivity) becomes reduced consistent with the increased basal 2,5AS activity in trisomy 21 cells compared with control cells.
Gerdes
A M
AM
Department of Clinical Chemistry, Odense University Hospital, Denmark.
Hørder
M
M
Bonnevie-Nielsen
V
V
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004314:Down Syndrome / Q000188:drug therapy / Q000201:enzymology*; D005260:Female; D006801:Humans; D007223:Infant; D007370:Interferon Type I / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D017471:Receptors, Interferon / Q000378:metabolism; D011994:Recombinant Proteins
D007370:Interferon Type I; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D015088:2',5'-Oligoadenylate Synthetase