High albumin levels restrict the kinetics of 13-cis retinoic acid uptake and intracellular isomerization to all-trans retinoic acid and inhibit its anti-proliferative effect on SZ95 sebocytes.
13-cis Retinoic acid is rapidly absorbed into cells and exerts its anti-proliferative effect on human sebocytes by specific isomerization to high levels of all-trans retinoic acid and binding the retinoic acid receptors. In this study, we have shown that bovine serum albumin, an extracellular binding protein for 13-cis retinoic acid, plays an important part in the uptake of 13-cis retinoic acid in human sebocytes, its intracellular isomerization to all-trans retinoic acid, and the induction of its anti-proliferative effect. The addition of highly concentrated bovine serum albumin (20 mg per ml) to the serum-free maintenance medium resulted in a rather controlled uptake of constant levels of 13-cis and all-trans retinoic acid into the cells over the 72 h of treatment. As a consequence, significantly reduced and delayed isomerization of 13-cis retinoic acid to all-trans retinoic acid was detected. In parallel experiments, the anti-proliferative activity of 13-cis retinoic acid on SZ95 sebocytes was abrogated by adding 20 mg bovine serum albumin per ml into the serum-free medium. These results indicate a critical function of serum albumin as retinoid-binding protein in reducing the concentration of active retinoids and restricting their biologic effects on human sebocytes.
Tsukada
Miki
M
Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Fabeckstrasse 60-62, 14195 Berlin, Germany.
Schröder
Mandy
M
Seltmann
Holger
H
Orfanos
Constantin E
CE
Zouboulis
Christos C
CC
D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D004347:Drug Interactions; D006801:Humans; D007536:Isomerism; D015474:Isotretinoin / Q000737:chemistry / Q000493:pharmacokinetics*; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D012867:Skin / Q000166:cytology* / Q000378:metabolism; D014212:Tretinoin / Q000737:chemistry / Q000378:metabolism*
D012710:Serum Albumin, Bovine; D014212:Tretinoin; D015474:Isotretinoin