The influence of the defection of fragile X mental retardation-1 gene on cyclic adenosine monophosphate / 中华神经科杂志

ABSTRACT

Objective To study the influence of defection of Fragile X mental retardation-1 gene (FMR1) on cyclic adenosine monophosphate (cAMP) and to discuss its mechanism. Methods FMR1 gene of peripheral blood mononuclear cell was silenced in vitro by sodium nitrointroprusside. The effect of gene-silencing was detected using reverse transcript polymerase chain reaction (RT-PCR). The specific activity of adenylate cyclase and phosphodiesterase was showed by the activity ratio of yield or consumption of cAMP during a unit time. Spectrophotometry was used to measure the two key enzymes (adenylate cyclase and phosphodiesterase), as to determining the level of intracellular cyclic adenosine monophosphate in the process of cAMP metabolism. Results FMR1 gene was fully silenced by sodium nitrointroprusside at 12th, 24th and 48th hour separately, re-expressed at 72th hour. If the cultivated fluild was replaced with new sodium nitrointroprusside at 48th hour, FMR1 gene would be silenced continuously. The intracellular cAMP level in the gene silenced group was lower, and significant depression of adenylate cyclase specific activity was found in the FMR1 gene silenced group (P=0.000). No significant difference was found on phosphodiesterase specific activity (P=0.983). Conclusions The results suggest that the yield of cAMP could be influenced by defection of FMR1. The depression of adenylate cyclase activity might be one of the causes of the decrease of intracellular cAMP production.