Specifically decreased collagen biosynthesis in scurvy dissociated from an effect on proline hydroxylation and correlated with body weight loss. In vitro studies in guinea pig calvarial bones.

Abstract

A B S T R A C T The question whether ascorbate regulates collagen production solely through its direct role in proline hydroxylation was investigated. Proteins in calvarial bones from control and scorbutic weanling guinea pigs were labeled in short-term cultures with radioactive proline. Proteins were digested with purified bacterial collagenase to distinguish between effects on collagen polypeptide production and hydroxyproline formation. There was a preferential decrease in the absolute rate of collagen biosynthesis beginning after 2 wk of ascorbate deficiency, and this effect was temporally dissociated from decreased proline hydroxylation. There were no significant changes in the absolute rates of collagen degradation or noncollagen protein production. In vitro inhibition of proline hydroxylation in normal bone with a,a'-dipyridyl did not affect the relative rate of collagen synthesis, further dissociating these functions. Ascorbate added to scorbutic bone cultures reversed defective proline hydroxylation but not defective collagen synthesis, suggesting that the latter was an indirect effect of scurvy. There was a linear correlation between the extent of body weight lost during the 3rd and 4th wk of scurvy and the rate of collagen synthesis in scorbutic bone. This correlation also applied to control animals receiving ascorbate, but with weight loss induced by food restriction. These studies establish for the first time that ascorbate deficiency in guinea pigs leads to a specific decrease in collagen polypeptide synthesis and suggest that this decrease results from the reduced food intake and/or weight-loss characteristic of scurvy.

Hepatocyte collagen production in vivo in normal rats.

“…Fractions (0.7 ml) were collected at a flow rate of 0.35 ml/min; elution of proteins was monitored using dual label techniques (17)(18)(19)(20). SDS-polyacrylamide gel electrophoresis (PAGE) was used to assess protein purification (21).…”

Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model

“…The ability of ascorbic acid to serve as a cofactor for prolyl and lysyl hydroxylases, important for collagen synthesis, is well known (5,6). In addition, ascorbate stimulates steadystate messenger RNA synthesis of a number of cartilage matrix components, including type I collagen (7), type II collagen (8,9), the alpha subunit of prolyl 4-hydroxylase (9), lysyl hydroxylase (6), and aggrecan (9).…”

The correlation of histopathological subcutaneous adipose tissue changes with post bariatric wound healing complications

“…21,22,23 There is deterioration in the extracellular matrix, likely attributed to the constant inflammation and its degrading effect on the skin tissue, possibly leading to wound complications. Changes also take place in the subcutaneous fat, demonstrating poorly defined lobules and more tenuous fibrous attachments to the deep dermis.…”