COMPARISON OF THE UPTAKE OF RETINOIDS 13-CIS-RETINOIC ACID AND RO-13-6298 DELIVERED TO HL-60 CELLS BY SERUM-ALBUMIN OR LOW-DENSITY-LIPOPROTEIN

Retinoids, a class of polyisoprenoids including retinol and retinoic a cid, regulate and control diverse physiological functions via their ce ll-differentiating and morphogenic potential. In the present study we showed that the extracellular concentration of retinoid-binding protei ns such as albumin limits the amount of retinoid entering the human pr omyelocytic leukemia cell line HL-60. These cells accumulate 5-10 time s more retinoid when delivered free in solution than when bound to eit her albumin or low-density lipoprotein (LDL). Moreover, the effect of protein binding is concentration-dependent, with a higher concentratio n of binding protein corresponding to a lower level of cellular uptake . Furthermore, the uptake of the ester derivative is higher than that of the acidic retinoid. These observations suggest that (a) the cellul ar uptake of both retinoids occurs via the free form of the ligand in solution, with the free concentration of ligand decreasing as the carr ier-protein concentration increases, and (b) according to a passive me chanism, the ester derivative, unionized and lipophilic, enters the ce lls more easily than does the acidic derivative.