Induction of collagen synthesis by ascorbic acid. A possible mechanism.
L-Ascorbic acid stimulates procollagen synthesis in cultured human skin fibroblasts without appreciably altering noncollagen protein synthesis. The effect is unrelated to intracellular degradation of newly synthesized procollagen. Levels of mRNA for pro alpha 1(I), pro alpha 2(I), and pro alpha 1(III), measured by hybridization with the corresponding cDNA probes, are elevated in the presence of ascorbic acid, whereas the level of mRNA for fibronectin is unchanged. Levels of functional mRNA for procollagen, measured in a cell-free translation assay, are specifically increased in the presence of ascorbic acid. Thus, ascorbic acid appears to control the expression of three different procollagen genes, each of which is located on a separate chromosome. It is proposed that intracellularly accumulated procollagen in ascorbate deficiency may lead to a translational repression of procollagen synthesis. Ascorbic acid may relieve this block by promoting hydroxyproline formation and, consequently, secretion of procollagen from the cell. The increased level of procollagen mRNA under the influence of ascorbic acid may be secondary to increased synthesis of procollagen polypeptides; the control point may be gene transcription or mRNA degradation.
Pinnel
S R
SR
Department of Medicine, Duke University Medical Center, Durham, NC.
Murad
S
S
Darr
D
D
D000375:Aging / Q000187:drug effects / Q000378:metabolism; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D006801:Humans; D011347:Procollagen / Q000378:metabolism; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D011347:Procollagen; D012333:RNA, Messenger; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; D001205:Ascorbic Acid