title: Ascorbate differentially regulates elastin and collagen biosynthesis in vascular smooth muscle cells and skin fibroblasts by pretranslational mechanisms.
abstract: Ascorbate contributes to several metabolic processes including efficient hydroxylation of hydroxyproline in elastin, collagen, and proteins with collagenous domains, yet hydroxyproline in elastin has no known function. Prolyl hydroxylation is essential for efficient collagen production; in contrast, ascorbate has been shown to decrease elastin accumulation in vitro and to alter morphology of elastic tissues in vivo. Ascorbate doses that maximally stimulated collagen production (10-200 microM) antagonized elastin biosynthesis in vascular smooth muscle cells and skin fibroblasts, depending on a combination of dose and exposure time. Diminished elastin production paralleled reduced elastin mRNA levels, while collagen I and III mRNAs levels increased. We compared the stability of mRNAs for elastin and collagen I with a constitutive gene after ascorbate supplementation or withdrawal. Ascorbate decreased elastin mRNA stability, while collagen I mRNA was stabilized to a much greater extent. Ascorbate withdrawal decreased collagen I mRNA stability markedly (4.9-fold), while elastin mRNA became more stable. Transcription of elastin was reduced 72% by ascorbate exposure. Differential effects of ascorbic acid on collagen I and elastin mRNA abundance result from the combined, marked stabilization of collagen mRNA, the lesser stability of elastin mRNA, and the significant repression of elastin gene transcription.
authors.affiliation: Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2561, USA. davidsjm@ctrvax.vanderbilt.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Davidson
authors.forename: P A
authors.initials: PA
authors.lastname: LuValle
authors.forename: O
authors.initials: O
authors.lastname: Zoia
authors.forename: D
authors.initials: D
authors.lastname: Quaglino
authors.forename: M
authors.initials: M
authors.lastname: Giro
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D003238:Connective Tissue / Q000378:metabolism; D004549:Elastin / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000378:metabolism*; D013552:Swine; D014158:Transcription, Genetic / Q000187:drug effects; D014333:Tropoelastin / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D014333:Tropoelastin; D003094:Collagen; D004549:Elastin; D001205:Ascorbic Acid