Expression and localization of sterol 27-hydroxylase (CYP27A1) in monkey retina.
Sterol 27-hydroxylase (CYP27A1) is a mitochondrial P-450 enzyme with broad substrate specificity for C27 sterols including 7-ketocholesterol (7kCh). CYP27A1 is widely expressed in human tissues but has not been previously demonstrated in the retina. In this study, we examined the expression and localization of CYP27A1 in the monkey retina where it localized mainly to the photoreceptor inner segments. CYP27A1 was also observed in Müller cells with faint immuno staining detected in the RPE and choriocapillaris. We also determined that the 27-hydroxylation of 7-ketocholesterol (27OH7kCh) rendered it non-toxic to cultured RPE cells. Moreover, the 27OH7kCh when mixed with 7-ketocholesterol significantly reduced the toxicity of 7-ketocholesterol. These data, when taken in context of the known functions of CYP27A1 imply that expression in the retina serves to modify the biological activity of oxidized sterols that are either transported or generated locally by photo-oxidation.
Section on Mechanisms of Retinal Diseases, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Jung Wha
JW
Lee
Hirotoshi
H
Fuda
Norman B
NB
Javitt
Charles A
CA
Strott
Ignacio R
IR
Rodriguez
D000818:Animals; D002478:Cells, Cultured; D053493:Cholestanetriol 26-Monooxygenase; D004791:Enzyme Inhibitors / Q000378:metabolism; D006900:Hydroxylation; D007150:Immunohistochemistry / Q000379:methods; D007653:Ketocholesterols / Q000378:metabolism; D008253:Macaca mulatta; D020419:Photoreceptor Cells, Vertebrate / Q000737:chemistry; D010857:Pigment Epithelium of Eye / Q000737:chemistry; D012160:Retina / Q000737:chemistry*; D013250:Steroid Hydroxylases / Q000032:analysis*
D004791:Enzyme Inhibitors; D007653:Ketocholesterols; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C003001:7-ketocholesterol