出版社：American Society for Biochemistry and Molecular Biology
摘要：We investigated the effects of two natural dietary retinoidX receptor (RXR) ligands, phytanic acid (PA) and docosahexaenoicacid (DHA), on proliferation and on the metabolism of retinol(vitamin A) in both cultured normal human prostate epithelialcells (PrECs) and PC-3 prostate carcinoma cells. PA and DHAinhibited the proliferation of the parental PC-3 cells and PC-3cells engineered to overexpress human lecithin:retinol acyltransferase(LRAT) in both the absence and presence of retinol. A syntheticRXR-specific ligand also inhibited PC-3 cell proliferation,whereas all-trans retinoic acid (ATRA) did not. PA and DHA treatmentincreased the levels of retinyl esters (REs) in both PrECs andPC-3 cells and generated novel REs that eluted on reverse-phaseHPLC at 54.0 and 50.5 min, respectively. Mass spectrometricanalyses demonstrated that these novel REs were retinyl phytanate(54.0 min) and retinyl docosahexaenoate (50.5 min). NeitherPA nor DHA increased LRAT mRNA levels in these cells. In addition,we demonstrate that retinyl phytanate was generated by LRATin the presence of PA and retinol; however, retinyl docosahexaenoatewas produced by another enzyme in the presence of DHA and retinol.Supplementary key words mass spectrometry • postsource decay • retinoid metabolism • lecithin:retinol acyltransferase
Abbreviations: ARAT, acyl-coenzyme A:retinol acyltransferase; ATRA, all-trans retinoic acid; DGAT1, acyl-coenzyme A:diacylglycerol acyltransferase 1; DHA, docosahexaenoic acid; HPRT, hypoxanthine guanine phosphoribosyl transferase; LDI, laser desorption ionization; LRAT, lecithin:retinol acyltransferase; MS, mass spectrometry; PA, phytanic acid; PrEC, normal human prostate epithelial cell; PSD, postsource decay; RAR, retinoic acid receptor; RE, retinyl ester; ROH, all-trans retinol; RP, retinyl palmitate; RXR, retinoid X receptor
