Alteration of amino acid transport by hydrocortisone. Different effects in human fibroblasts derived from normal skin and keloid.
The rate of proline transport increases significantly when human dermal fibroblasts are grown with 1.5 microM hydrocortisone. Fibroblasts derived from keloid tissue are significantly more stimulated than normal fibroblasts. An average increase of 41% is obtained with 8 normal strains, whereas uptake in 8 keloid-derived strains increases 210%. Similar results are obtained with the system A amino acid analogue 2-(methylamino)isobutyric acid, for which the uptake rate increases 87% and 329% in normal and keloid cells, respectively. The hydrocortisone-mediated increase in proline transport and the difference between keloid and normal fibroblasts are observed throughout the culture cycle and after depletion of amino acid pools. The uptake of nine other amino acids are differentially altered in normal and keloid cells. Competition experiments with 2-(methylamino)isobutyric acid indicate that the greatest differences occur with amino acids that are transported preferentially by the A system. Inhibition of the hydrocortisone-mediated increase by progesterone and a lag period of approximately 3 h indicate that hydrocortisone is regulating proline transport by a cytosolic receptor mechanism.
D000596:Amino Acids / Q000378:metabolism* / Q000494:pharmacology; D000621:Aminoisobutyric Acids / Q000031:analogs & derivatives / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002453:Cell Cycle; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007627:Keloid / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D011392:Proline / Q000378:metabolism
D000596:Amino Acids; D000621:Aminoisobutyric Acids; C017911:2-(methylamino)isobutyric acid; D011374:Progesterone; D011392:Proline; D001205:Ascorbic Acid; D006854:Hydrocortisone