Procollagen genes

Osteogenesis imperfecta is a good example of a disease in which locus heterogeneity (choice C) is observed, but this principle refers to the fact that a mutation in either the type 1 procollagen gene on chromosome 7 or the type 1 procoUagen gene on chromosome 17 can result in imperfect formation of the trimeric protein. This principle does not explain the co-occurrence of ftactures and blue sclerae. 

Ascorbate can also serve as a signal. In cultured cells, which are usually deficient in vitamin C, addition of ascorbate causes an enhanced response to added iron, inducing synthesis of the iron storage protein ferritin.11 Ascorbate indirectly stimulates transcription of procollagen genes 1 and decreases secretion of insulin by the pancreas.)) However, since its concentration in blood is quite constant this effect is not likely to cause a problem for a person taking an excess of vitamin C. 

Kayano, K., Sakaida, I., Uchida, K., Okita, K. Inhibitory effects of the herbal medicine Sho-saiko-to (TJ-9) on cell proliferation and procollagen gene expressions in cultured rat hepatic stellate cells. J. Hepatol. 1998 29 642-649... 

Iyer SN, Gurujeyalakshmi G, Giri SN. 1999. Down regulation of procollagen genes at the transcriptional level in the bleomycin-induced model of lung fibrosis. J. Pharmacol. Exp. Ther. 289 211-18... 

Gadson PF, Dalton ML, Patterson E, Svoboda DD, Hutchinson L, Schram D, Rosenquist TH (1997) Differential response of mesoderm- and neural crest-derived smooth muscle to TGppi regulation of c-myb and al (I) procollagen genes. Exp Cell Res 230 169-180... 

Upholt, W.B. Sandell, L.J. (1986). Exon/intron organization of the chicken type II procollagen gene intron size distribution suggests a minimal intron size. IVoc. Natl Acad. Sci. USA, 83, 2325-9. 

The two- to threefold increase in the transcription level induced by ascorbic acid is too small to identify the ascorbic acid regulatory sequence(s) on the procollagen gene by conventional analysis methods. Further work is required to develop cell culture systems in which the procollagen gene can be induced at much higher levels. 

The definite mechanism by which ascorbic acid stimulates transcription of the procollagen gene remains unknown. However, an alternative hypothesis as to the role of ascorbic acid as a peroxidant is that ascorbic acid stimulates lipid peroxidation with the formation of reactive aldehydes, which up-regulate expression of the procollagen gene. This is based on the following observations ... 

Type I collagen molecules are heterotrimeric molecules with an a chain composition of two al (I) chains and one o 2(I) chain from the COLlAl and COLl A2 genes, respectively. This a chain composition is written as [a 1(1)] 20 2 (I). A type I collagen molecule is synthesized as a procollagen type I molecule. The N- and C-terminal propeptides are cleaved as part of the processing in tissues and are called N- and C-propeptides, respectively. The human pro-o (I) and pro-o 2(I) have 246 and 247 residues in their C-propeptides, respectively. The C-propeptide contains interchain disulfide bonds, which are important for the stabilization of the three a chains in the endoplasmic reticulum (ER). 

It modulates the three genes responsible for the synthesis of procollagen leading to an increase in type III collagen synthesis. This action is very important for post-peel healing and maintaining normal skin structure. 

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