Cyclic Guanosine Monophosphate Metabolism in Human Amnion Cells Trisomic for Chromosome 21

Abstract

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.