Cyclic guanosine monophosphate metabolism in human amnion cells trisomic for chromosome 21.
An extra copy of chromosome 21, a small chromosome or a specific segment of it, is the cause of the disorder known as Down's syndrome (DS). Genes mapped to this chromosome include superoxide dismutase-1 (SOD-1) along with other enzymes. Gene dosage effects have been shown for some of these enzymes, including SOD-1. Increased SOD-1 has been suggested to stimulate the cGMP-forming enzyme, guanylate cyclase (GC). In the present study we have used amnion cells from DS subjects and normal subjects in order to indirectly test the effects of SOD-1 on the cGMP metabolism. We have measured the cAMP and cGMP content, SOD-1 activity, GC activity and cGMP phosphodiesterase (G-PDE) activity in amnion cells from DS subjects and normal subjects, respectively. The levels of cGMP in DS amnion cells were lower than in normal cells, although the SOD-1 activity was higher in DS amnion cells. Furthermore, the GC activity and the G-PDE activity were found to be lower in the trisomic cells. Our results do not support the suggestion that SOD-1 has a stimulatory effect on the GC activity.
Karlsson
J O
JO
Department of Pharmacology, University Hospital, Linköping, Sweden.
Sjöstedt
A
A
Wahlström
J
J
Axelsson
K L
KL
Andersson
R G
RG
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000032:analysis; D000650:Amnion / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004314:Down Syndrome / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D013482:Superoxide Dismutase / Q000494:pharmacology
D003574:Cytochrome c Group; C083951:cytochrome c553; C022302:cytochrome C-552; D000242:Cyclic AMP; D013482:Superoxide Dismutase; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP