Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003969 (vitamin C deficiency)
 625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chick embryo chondrocytes cultured in sera from scorbutic and fasted guinea pigs exhibited decreases in collagen and proteoglycan production to about 30-50% of control values (I. Oyamada et al., 1988, Biochem. Biophys. Res. Commun. 152, 1490-1496). Here we show by pulse-chase labeling experiments that in the chondrocyte system, as in the cartilage of scorbutic and fasted guinea pigs, decreased incorporation of precursor into collagen was due to decreased synthesis rather than to increased degradation. There was a concomitant decrease in type II procollagen mRNA to about 32% of the control level. As in scorbutic cartilage, proteoglycan synthesis by chondrocytes in scorbutic serum was blocked at the stage of glycosaminoglycan chain initiation. Scorbutic and fasted guinea pig sera also caused a 50-60% decrease in the rates of collagen and proteoglycan synthesis in adult human skin fibroblasts, which synthesize mainly type I collagen. Decreased matrix synthesis in both cell types resulted from the presence of an inhibitor in scorbutic and fasted sera. Elevated cortisol levels in these sera were not responsible for inhibition, as determined by the addition of dexamethasone to chondrocytes cultured in normal serum. Insulin-like growth factor I (IGF-I, 300-350 ng/ml) reversed the inhibition of extracellular matrix synthesis by scorbutic and fasted guinea pig sera in both cell types and prevented the decrease in type II procollagen mRNA in chondrocytes. Therefore, in addition to its established role in proteoglycan metabolism, IGF-I also regulates the synthesis of several collagen types. An increase in the circulating inhibitor of IGF-I action thus could lead to the negative regulation of collagen and cartilage proteoglycan synthesis that occurs in ascorbate-deficient and fasted guinea pigs.
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PMID:Scorbutic and fasted guinea pig sera contain an insulin-like growth factor I-reversible inhibitor of proteoglycan and collagen synthesis in chick embryo chondrocytes and adult human skin fibroblasts. 229 32

We previously proposed that the decreased rates of synthesis of collagen and proteoglycans in vitamin C-deficient guinea pigs were unrelated to the role of ascorbate in proline hydroxylation but might result from modulation of hormones known to change during fasting. In the present studies, we found that sera from guinea pigs on an ascorbate-free diet for 24-28 days or from those fasted for 4 days, with vitamin C supplementation, showed similar changes in the concentrations of several hormones. EGF and IGF-II concentrations were unchanged, but cortisol was increased 3-5 times and growth hormone was increased to approximately twice normal levels. Thyroxine and IGF-I concentrations were decreased to 40% and 25-33% of normal levels, respectively. The decrease in serum IGF-I must occur by a growth hormone-independent pathway. The extent of changes in hormone concentrations in sera from ascorbate-deficient guinea pigs was correlated with the extent of weight loss. Sera from scorbutic and fasted guinea pigs failed to stimulate DNA synthesis in quiescent BALB 3T3 cells in the presence of saturating concentrations of EGF and PDGF. Addition of experimental sera to normal serum showed that lack of mitogenic activity was due to the presence of an inhibitor. Inhibition was not related to IGF-I concentrations in the sera, although it was reversed by the addition of IGF-I to sera from scorbutic or fasted animals. These results support our proposed model and suggest that IGF-I, as well as an inhibitor of its activity, plays a role in the regulation of growth by vitamin C and other nutrients.
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PMID:Similar hormonal changes in sera from scorbutic and fasted (vitamin C-supplemented) guinea pigs, including decreased IGF-I and appearance of an IGF-I reversible mitogenic inhibitor. 262 79

Acutely scorbutic and fasted (vitamin C-supplemented) guinea pigs exhibit decreased collagen gene expression associated with weight loss. We recently demonstrated that circulating insulin-like growth factor-binding protein-1 and -2 (IGFBP-1 and -2) are induced in these deficiencies, and that removal of IGFBP-1 and -2 from serum of such animals by specific antibodies reverses inhibition of cellular IGF-I-dependent functions, including collagen and DNA synthesis. Here we investigated the kinetics of induction of IGFBP-1 and -2 relative to suppression of collagen gene expression. Guinea pigs were fasted for 10-96 h, with 3-24% weight loss, or received an ascorbate-free diet for up to 4 weeks, with 5-28% weight loss during the third and fourth weeks (phase II of scurvy). In both deficiencies, there was noncoordinate regulation of collagen mRNA expression in tissues. Type I collagen mRNA concentrations in skin decreased rapidly after 5-10% weight loss and reached about 10% of normal levels, whereas in bone, there was a later, and not as extensive, decrease. The concentration of cartilage type II collagen mRNA decreased rapidly initially, but then remained at 40-50% of normal. Circulating IGF-I concentrations remained normal during the period when collagen gene expression was initially suppressed, although there was a later decrease. In contrast, mRNAs for IGFBP-1 and -2 and the circulating proteins were induced before or concomitantly with the suppression of collagen gene expression. The ability of fasted or scorbutic guinea pig sera to inhibit IGF-I action in cells increased in parallel with IGFBP activity ([125I]IGF-I binding), which, in turn, mainly reflected the concentration of IGFBP-1 in sera. Serum insulin may be the primary regulator of the IGFBPs. Its levels were decreased to 10-13% of normal when weight loss commenced, whereas cortisol levels, although increased, did not correlate with the induction of IGFBPs. The overall results taken together with our recent findings from cell culture experiments are compatible with circulating IGFBP-1 and -2 acting as inhibitors of collagen gene expression by blocking IGF-I action during fasting and phase II of vitamin C deficiency.
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PMID:Evidence for an in vivo role of insulin-like growth factor-binding protein-1 and -2 as inhibitors of collagen gene expression in vitamin C-deficient and fasted guinea pigs. 750 38

Collagen gene expression and proteoglycan synthesis are decreased in vitamin C-deficient guinea pigs losing weight and in fasted guinea pigs receiving ascorbate. Sera from such guinea pigs contain an insulin-like growth factor (IGF)-I-reversible inhibitor of collagen, proteoglycan and DNA synthesis and elevated levels of 29 and 35-kDa IGF binding proteins (IGFBPs). We now have identified the induced proteins as IGFBPs 1 and 2 and investigated their role as inhibitors. Guinea pig sera were treated with antibodies to IGFBPs 1 and 2 and antibody-IGFBP complexes were removed by passage through a Protein A-Sepharose column. Inhibitor content of fasted and scorbutic sera, and Protein A pass-through fractions derived from them, was assessed by their level of stimulation of DNA and collagen synthesis in 3T3 cells, compared to analogously treated normal guinea pig serum. Removal of IGFBP-1 from scorbutic serum reversed inhibition of collagen and DNA synthesis by more than half but removal of IGFBP-2 was less effective. Removal of both IGFBPs reversed inhibition almost completely. Similar results were obtained with fasted guinea pig serum. Conversely, purified rat IGFBPs 1 and 2 inhibited DNA and collagen synthesis in cells cultured in normal guinea pig serum or IGF-I-stimulated DNA synthesis, with IGFBP-1 being more potent. Thus, IGFBP-1 and, to a lesser extent IGFBP-2, cause inhibition of IGF-I action by sera from fasted and scorbutic guinea pigs and may inhibit collagen gene expression in vivo.
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PMID:Circulating insulin-like growth factor binding proteins (IGFBPs) 1 and 2 induced in vitamin C-deficient or fasted guinea pigs inhibit IGF-I action in cultured cells. 752 15

The effects of streptozotocin-induced diabetes on proteolytic activity and collagen biosynthesis in skin lesions in rats and on IGF-I binding proteins in their serum were evaluated. It was found that both collagen in intact skin and collagen biosynthesis in skin lesions were lower compared to control animals. Concurrently, there was an increase in proteolytic activity both in intact and lesioned skin. The livers and sera of diabetic animals also showed higher proteolytic activity. Inhibitors of cathepsin D (pepstatin and potato-derived inhibitor) prevent the decrease of collagen biosynthesis in the skin of diabetic rats. These observations indicate the co-existence of two phenomena in the investigated animals: an increase in proteolytic activity in tissues and a decrease in collagen biosynthesis. Furthermore, the diabetic rats showed significant changes in the composition of IGF-I serum binding proteins. The amount of high molecular weight binding proteins (HMW-BPs) was distinctly decreased, whereas the content of low molecular weight binding proteins (LMW-BPs) was significantly increased. Large amounts of LMW-BPs have been previously found in the sera of fasted and scorbutic animals. They are inhibitors of IGF-I activity. It is suggested that the increase in LMW-BP concentration in diabetic serum may be responsible for the inactivation of IGF-I resulting in decreased collagen biosynthesis. The role of proteolysis in the production of LMW-BPs in diabetic serum is discussed.
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PMID:Changes in IGF-binding proteins in rats with experimental diabetes. 816 86