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Biomedical subjects

R S Bhatnagar

Publications and source records attributed to R S Bhatnagar.

At least 73 records · Page 4Linked to original sources
PubMed1975

Loss of ability to synthesize collagen in fibroblasts transformed by rous sarcoma virus.

Transformation of chick embryo fibroblasts by Rous sarcoma virus inhibited their ability to synthesize collagen. Kinetic experiments showed that 72 hours after infection, collagen synthesis was reduced by 90%. Nontransforming Rous-associated viruses did not inhibit collagen synthesis. The inhibition resulted from the failure of the cells to synthesize collagen polypeptides rather than from a decrease in the activity of prolyl hydroxylase; the levels of prolyl hydroxylase were fourfold those in uninfected cells. The addition of dibutyryl cyclic AMP and theophylline, alone or together, did not restore collagen synthesis.

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PubMed1967

Intracellular pool of unhydroxylated polypeptide precursors of collagen.

The hydroxyproline and hydroxylysine in collagen are synthesized by an apparently unique pathway in which proline and lysine are hydroxylated after they are incorporated into a large polypeptide precursor of collagen called protocollagen. When the hydroxylation of protocollagen in isolated tissues is intermittently interrupted, hydroxylation can occur after complete polypeptides are released from ribosomal complexes. Cartilage from chick embryos was incubated with the iron chelator alpha,alpha'-dipyridyl for 2 hours to inhibit protocollagen hydroxylase, and then the inhibition was reversed by transferring the tissues to medium containing ferrous iron and no alpha,alpha'-dipyridyl. "Pulse labeling" of the tissues during these two periods indicated that both the accumulated protocollagen and the polypeptides synthesized after reversal of the inhibition were hydroxylated at the same rate. Even when no measures are taken to inhibit the hydroxylation of protocollagen, most of the hydroxyproline in collagen is probably synthesized after complete protocollagen polypeptides are released from ribosomes.

Animals↗
PubMedDate not supplied

Increased prolyl hydroxylase activity and collagen synthesis in hepatocyte cultures exposed to superoxide.

Primary monolayer cultures of rat hepatocytes at confluence were exposed to an exogenously added source of superoxide, and its influence on collagen synthesis was examined. Superoxide was generated by the addition of dihydroxyfumarate to the culture medium. Exposure of hepatocytes to dihydroxyfumarate greatly stimulated the activity of prolyl hydroxylase and the synthesis of collagen. A significant increase in prolyl hydroxylase activity was observed with 5 micrograms per ml dihydroxyfumarate in 24 hr relative to that in the untreated cultures. Maximum stimulation of greater than 3-fold compared to the control value was elicited by 25 micrograms per ml dihydroxyfumarate. When scavengers of superoxide such as superoxide dismutase and Cu(Lys)2 were added in the medium, the increase in prolyl hydroxylase activity induced by dihydroxyfumarate was nearly abolished. Experiments with actinomycin D indicated that synthesis of new RNA was involved in the stimulation of prolyl hydroxylase activity. Analysis of collagen synthesis in cultures exposed to dihydroxyfumarate also showed a marked increase compared to that of the untreated cultures. The presence of superoxide dismutase in the medium significantly reduced the increase in collagen synthesis. Our results indicate that superoxide mediates the stimulation of collagen synthesis in hepatocytes. These findings may provide a possible explanation for excess collagen formation during induced liver fibrosis.

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