Studies on the transcriptional regulation of cholesterol 24-hydroxylase (CYP46A1): marked insensitivity toward different regulatory axes.

摘要: Mammalian CNS contains a disproportionally large and remarkably stable pool of cholesterol. Despite an efficient recycling there is some requirement for elimination brain Conversion cholesterol into 24S-hydroxycholesterol by the 24-hydroxylase (CYP46A1) quantitatively most important mechanism. Based on protein expression plasma levels 24S-hydroxycholesterol, CYP46A1 activity appears to be highly in adults. Here we have made structural functional characterization promoter human gene. No canonical TATA or CAAT boxes were found region. Moreover this region had high GC content, feature often genes considered largely housekeeping function. A broad spectrum regulatory axes using variety constructs did not result significant transcriptional regulation. Oxidative stress caused increase activity. The possibility substrate-dependent regulation was explored vivo sterol-deficient mouse model (Dhcr24 null) which almost all been replaced with desmosterol, substrate CYP46A1. Compared heterozygous littermates no statistically difference mRNA Cyp46a1. During first 2 weeks life wild-type mouse, however, Cyp46a1 found, parallel level reduction synthesis. failure demonstrate under conditions discussed relation turnover neuronal