Hydrocortisone induction of system A amino acid transport in human fibroblasts from normal dermis and keloid.
The rate of proline transport increases when human dermal fibroblasts are grown in physiological levels of hydrocortisone. This response to hydrocortisone is significantly greater in fibroblasts derived from keloids, benign dermal tumors caused by an inherited abnormality in wound healing (Russell, S. B., Russell, J. D., and Trupin, J. S. (1982) J. Biol. Chem. 257, 9525-9531). We report here that increased transport activity is largely accounted for by an increase in Vmax of the System A component of proline uptake; this stimulation is 1- to 2-fold in normal fibroblasts and 5- to 10-fold in keloid-derived cells. Similar results are obtained with 2-(methylamino)isobutyric acid, a specific substrate of System A transport, and for the System A components of glycine and alanine uptake. The stimulatory effect of the hormone is blocked by cycloheximide and actinomycin D in both keloid and normal cells. Hydrocortisone did not alter the measured membrane potential in either cell type. These data suggest that hydrocortisone induces a protein specifically involved in System A amino acid transport. Keloid cells may provide a unique opportunity to study this protein.
D000596:Amino Acids / Q000378:metabolism*; D000621:Aminoisobutyric Acids / Q000378:metabolism; D001693:Biological Transport, Active; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007627:Keloid / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009861:Onium Compounds / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011392:Proline / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D007202:Indicators and Reagents; D009861:Onium Compounds; D009943:Organophosphorus Compounds; C017911:2-(methylamino)isobutyric acid; D011392:Proline; D012964:Sodium; C013289:tetraphenylphosphonium; D006854:Hydrocortisone