Abstract:
:CYP27A1, an enzyme with several important roles in cholesterol homeostasis and vitamin D₃ metabolism, has been ascribed anti-atherogenic properties. This study addresses an important problem regarding how this enzyme, involved in cholesterol metabolism in the liver and peripheral tissues, is regulated. Our results identify the human CYP27A1 gene as a new target for the JNK/c-jun pathway. Initial experiments showed that an inhibitor of c-Jun N-terminal kinase (JNK) downregulated basal CYP27A1 promoter activity whereas overexpression of JNK slightly enhanced promoter activity. Androgen receptor (AR)-mediated upregulation of mRNA levels and endogenous enzyme activity was recently reported. In the present study, the AR antagonist nilutamide blocked the androgen induction of CYP27A1. The present data revealed that inhibition of the JNK/c-jun pathway abolishes the AR-mediated effect on CYP27A1 transcription and enzyme activity, whereas overexpression of JNK markedly increased androgenic upregulation of CYP27A1. In conclusion, the current results indicate involvement of the JNK/c-jun pathway in AR-mediated upregulation of human CYP27A1. The link to JNK signaling is interesting since inflammatory processes may upregulate CYP27A1 to clear cholesterol from peripheral tissues.
journal_name
Arch Biochem Biophysjournal_title
Archives of biochemistry and biophysicsauthors
Norlin M,Pettersson H,Tang W,Wikvall Kdoi
10.1016/j.abb.2010.11.023subject
Has Abstractpub_date
2011-02-15 00:00:00pages
236-41issue
2eissn
0003-9861issn
1096-0384pii
S0003-9861(10)00496-0journal_volume
506pub_type
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