Randolph R K, Simon M
Living Skin Bank, University Hospital, Department of Oral Biology and Pathology, School of Dental Medicine, State University of New York, Stony Brook 11794,USA.
J Lipid Res. 1997 Jul;38(7):1374-83.
The uptake and metabolism of exogenous all-trans-retinoic acid by human epidermal keratinocytes in submerged culture was examined. Retinoic acid presented to keratinocytes in physiological form bound to albumin was rapidly taken up. Peak cellular concentrations were achieved within 1 h and were 50- to 100-fold higher than that in medium. Retinoic acid metabolism was less rapid but was vigorous, exhibiting a half-life of 6 h. Neither uptake nor metabolism was saturable at medium retinoic acid concentrations up to 1 microM. Eighty-five percent of retinoic acid was metabolized to unidentified polar compounds which were excreted from cells to the medium. The production and clearance of the polar metabolites was inhibited 60% by 10 microM ketoconazole. Fifteen percent of intracellular retinoic acid was converted to 3,4-didehydroretinoic acid, was proportional to cellular retinoic acid concentration, and was not affected by ketoconazole. Cellular retinyl ester content, which is sensitive to exogenous retinoic acid, was correlated with both the concentration and the quantity, of retinoic acid in the culture system. These results suggest that the metabolism of retinoic acid in keratinocytes is substrate limited and has potential to limit the availability of exogenous retinoic acid for retinoid signaling.
研究了人表皮角质形成细胞在浸没培养中对外源全反式维甲酸的摄取和代谢。与白蛋白结合以生理形式呈现给角质形成细胞的维甲酸被迅速摄取。在1小时内达到细胞内峰值浓度，比培养基中的浓度高50至100倍。维甲酸代谢速度较慢但较为活跃，半衰期为6小时。在培养基维甲酸浓度高达1 microM时，摄取和代谢均不饱和。85%的维甲酸代谢为未鉴定的极性化合物并从细胞分泌到培养基中。10 microM酮康唑可抑制极性代谢产物的产生和清除60%。15%的细胞内维甲酸转化为3,4-二脱氢维甲酸，与细胞维甲酸浓度成正比，且不受酮康唑影响。对外源维甲酸敏感的细胞视黄酯含量与培养系统中维甲酸的浓度和量均相关。这些结果表明，角质形成细胞中维甲酸的代谢受底物限制，有可能限制外源性维甲酸用于类视黄醇信号传导的可用性。
