脆性X综合征患儿细胞内环磷酸腺苷降低的机制

Mechanism of intracellular cyclic adenosine monophosphate level depression in fragile X syndrome

目的 探讨脆性X综合征细胞内环磷酸腺苷 (cAMP)降低的机制。方法 通过基因封闭方法 ,建立Fra(X)细胞模型 ,研究cAMP代谢途径中的两个关键酶腺苷酸环化酶 (AC)及磷酸二酯酶 (PDE)的活性变化。结果 试验组AC的比活力明显低于对照组 (P =0 .0 0 0 ) ,而PDE比活力则无显著改变 (P =0 .983 )。结论 Fra (X)细胞内cAMP水平的降低可能与AC活性的抑制有关 。

Objective To discuss the mechanism of intracellular cyclic adenosine monophosphate (cAMP) level depression in fragile X syndrome.Methods Two key enzymes(adenylate cyclase and phosphodiesterase) in the process of cAMP metabolism were detected after the FMR1 gene was silenced in vitro.Results Significant depression of adenylate cyclase specific activity was found in the FMR1 genesilenced group(P=0.000);No significant change was found on phosphodiesterase specific activity(P=0.983).Conclusion The inhibition of adenylate cyclase activity most likely to be the main cause of the intracellular cAMP level depression in fragile X syndrome.