Oxysterol 7α-Hydroxylase (CYP39A1) in the Ciliary Nonpigmented Epithelium of Bovine Eye

Abstract

SUMMARY:The CYP39A1 oxysterol 7␣-hydroxylase preferentially catalyzes the 7␣-hydroxylation of 24-hydroxycholesterol and has been suggested to play a role in the alternative bile acid synthesis pathway in the liver. The presence of CYP39A1 oxysterol 7␣-hydroxylase has been reported only in the liver. To investigate the physiologic characteristics of the ciliary processes in bovine ocular tissues, we raised a mAb, 42C, against nonpigmented epithelial (NPE) cells, which have tight junctions that act as a blood-aqueous barrier and are involved in producing aqueous humor and maintaining ocular homeostasis. Immunohistochemical analysis showed that 42C antibody reacted intensely with an antigen in the NPE cells of the ciliary processes but not with other ocular tissues. The SDS-PAGE profile of immunoaffinity-purified antigens from bovine ciliary processes showed a predominant protein of molecular mass of 44.0 kDa. The amino acid sequence of this antigenic protein was identical to human CYP39A1 oxysterol 7␣-hydroxylase. Immunoreactivity with 42C antibody was found only in hepatocytes and ocular tissues. These data suggest a new physiologic function for the CYP39A1 oxysterol 7␣-hydroxylase in addition to the production of bile acids and provide new insight into the physiologic role of the ciliary NPE cells concerning the metabolism of sterols in the eye. (Lab Invest 2003, 83:349 -355).

Transcriptional regulation of cholesterol 24-hydroxylase by histone deacetylase inhibitors

“…This cytochrome P450, which is a 7a-hydroxylase highly specific for 24S-hydroxycholesterol, was originally cloned as liver specific species [21]. Subsequent investigations have identified Cyp39a1 mRNA or protein in brain or the non-pigmented epithelium of the retina [23,24]. To the best of our knowledge, this is the first demonstration of pharmacological regulation of CYP39A1.…”

Cholesterol oxidation in the retina: implications of 7KCh formation in chronic inflammation and age-related macular degeneration

“…CYP7B1 is broadly expressed in many tissues and has high expression in tissues of neurological origin, but it has not been previously reported in the retina. CYP39A1 is mostly expressed in the liver but has also been reported in the bovine ciliary nonpigmented epithelium of the eye ( 44 ). The expression of CYP39A1 in the neural retina has not been previously reported.…”

Cerebrospinal Fluid Steroidomics: Are Bioactive Bile Acids Present in Brain?

“…The latter pathway is initiated in brain by 24(S)-hydroxylation of cholesterol by neuron-specific CYP46A1 (48), followed by 7␣-hydroxylation by the presumed liver-specific enzyme CYP39A1 (69). However, recent data indicate that CYP39A1 protein is also expressed in eye and its mRNA in brain (53,70), opening a route for extrahepatic bile acid biosynthesis via this pathway. In fact, all of the enzymes necessary for the biosynthesis of the primary bile acid chenodeoxycholic acid by the 24(S)-hydroxycholesterol pathway are expressed in brain (Scheme 4).…”