N-(4-hydroxyphenyl)-retinamide increases lecithin:retinol acyltransferase activity in rat liver.
N-(4-Hydroxyphenyl)-retinamide (4-HPR; Fenretinide) is a synthetic retinoid which is undergoing investigation as a cancer chemopreventive agent. However, 4-HPR alters vitamin A kinetics and reduces the concentration of plasma retinol. We have conducted studies to examine the effects of 4-HPR on the activity of the enzyme lecithin:retinol acyltransferase (LRAT). This enzyme is implicated in the absorption and storage of vitamin A and is regulated, in liver, by vitamin A nutritional status. To determine whether 4-HPR, like retinoic acid, is able to induce liver LRAT activity, vitamin A-deficient rats having negligible liver LRAT activity were treated with single doses of 4-HPR (0.02-2.5 mg) and liver homogenates were assayed for LRAT activity using 3H-retinol bound to the cellular-retinol binding protein, CRBP, as substrate. Treatment with 4-HPR resulted in a dose- and time-dependent increase in liver LRAT activity which reached a maximum at 24 h. The activity of LRAT assayed in vitro and of hepatic 3H-retinyl ester content determined after an in vivo pulse of 3H-retinol were highly correlated (r = 0.802, P < 0.0002). When vitamin A-sufficient rats were fed a 4-HPR-supplemented diet for 30 d, LRAT activity differed significantly from control values in the liver (P < 0.0001) but not the small intestines. Changes in hepatic retinol metabolism which favor the esterification of vitamin A may be related to the mechanism by which 4-HPR alters vitamin A kinetics in vivo.
Matsuura
T
T
Department of Biochemistry, Medical College of Pennsylvania, Philadelphia 19129, USA.
Zhao
Z
Z
Ross
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AC
D000217:Acyltransferases / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D017313:Fenretinide / Q000494:pharmacology*; D007421:Intestine, Small / Q000201:enzymology; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D014801:Vitamin A / Q000032:analysis / Q000097:blood / Q000378:metabolism; D014802:Vitamin A Deficiency / Q000378:metabolism
D000970:Antineoplastic Agents; D014801:Vitamin A; D017313:Fenretinide; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase