The metabolism of collagen in male rats made diabetic by treatment with either streptozotocin or alloxan was studied after the injection of 3H-proline by estimating specific and total 3H-hydroxyproline activity in skin collagen fractions and urine. Experimentally induced diabetes was found to decrease the neutral salt-soluble and acid-soluble collagen with no change in insoluble collagen as compared to a control group. The specific and total radioactivity of 3H-hydroxyproline in soluble and insoluble collagen fractions were also decreased. Studies of total 3H-hydroxyproline activities in soluble collagens and insoluble collagen showed that the conversion of soluble to insoluble collagen was influenced by diabetes. Both streptozotocin and alloxan were found to increase urinary excretion of total hydroxyproline and 3H-hydroxyproline during the first 12 h after the administration of 3H-proline. Weekly analyses of urinary hydroxyproline also indicated a similar pattern. The results of the present investigation clearly indicate decreased synthesis and increased catabolism of collagen accompanied by accelerated conversion of soluble to insoluble collagen in experimentally induced diabetes.

Alloxan↗

PubMedDate not supplied

Studies on biological macromolecules. V. Effect of acridine orange exposure on synthesis of nucleic acids and protein in a mammalian cell line in vitro.

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Acridines↗

PubMedDate not supplied

Regulation of proteasome complexes by gamma-interferon and phosphorylation.

Proteasomes play a major role in non-lysosomal proteolysis and also in the processing of proteins for presentation by the MHC class I pathway. In animal cells they exist in several distinct molecular forms which contribute to the different functions. 26S proteasomes contain the core 20S proteasome together with two 19S regulatory complexes. Alternatively, PA28 complexes can bind to the ends of the 20S proteasome to form PA28-proteasome complexes and PA28-proteasome-19S hybrid complexes have also been described. Immunoproteasome subunits occur in 26S proteasomes as well as in PA28-proteasome complexes. We have found differences in the subcellular distribution of the different forms of proteasomes. The gamma-interferon inducible PA28 alpha and beta subunits are predominantly located in the cytoplasm, while 19S regulatory complexes (present at significant levels only in 26S complexes) are present in the nucleus as well as in the cytoplasm. Immunoproteasomes are greatly enriched at the endoplasmic reticulum (ER) where they may facilitate the generation of peptides for transport into the lumen of the ER. We have also investigated the effects of gamma-interferon on the levels and subcellular distribution of inducible subunits and regulator subunits. In each case gamma-interferon was found to increase the level but not to alter the distribution. Several subunits of proteasomes are phosphorylated including alpha subunits C8 (alpha7) and C9 (alpha3), and ATPase subunit S4 (rpt2). Our studies have shown that gamma-interferon treatment decreases the level of phosphorylation of proteasomes. We have investigated the role of phosphorylation of C8 by casein kinase II by site directed mutagenesis. The results demonstrate that phosphorylation at either one of the two sites is essential for the association of 19S regulatory complexes and that the ability to undergo phosphorylation at both sites gives the most efficient incorporation of C8 into the 26S proteasome.

Animals↗