High expression level of homocitrulline is correlated with seborrheic keratosis and skin aging

Abstract Backgroud Homocitrulline (Hcit), is involved in the pathological processes of some diseases. However, the role and function of Hcit (CBL) in human skin remains largely obscure. Objective To investigate the correlation of the level of Hcit in seborrheic keratosis, skin aging, and its clinical significance. Methods Immunohistochemistry was used to analyze the level of Hcit in skin lesions of seborrheic keratosis (SK), unaffected skin (distant 0.5 centimeters from SK lesion), and normal skin of healthy subjects in the control group. ELISA test was used to detect the serum level of CBL in SK patients and healthy subjects of different ages. Results Hcit was mainly localized in the nucleus of epidermal cells. In healthy control skin, the expression of Hcit increased with age and showed a positive correlation with age (the correlation coefficient was 0.806, p = 0.0002). The expressional level of Hcit in SK lesions was higher than that in healthy control skin (Z = −3.703, p = 0.0002). The serum level of CBL in healthy subjects and in SK patients increased with age (the correlation coefficient were 0.5763, p = 0.0032; 0.682, p = 0.004. respectively). The serum level of CBL in SK patients was higher than that in healthy subjects (Z = −2.19, p = 0.030). Study limitations The small serum sample size in the study. Conclusion The high expressional level of Hcit is correlated with seborrheic keratosis and skin aging. HCit may be one of the potential biomarkers of skin aging.

Research progress on the relationship between plasma protein carbamylation and chronic kidney disease / 中华临床营养杂志

Plasma protein carbamylation may change the structure of protein , thus influencing its function.Carbamylation is mainly through combination of cyanate with protein , which is elevated in patients with chronic kidney disease mainly because cyanate level is raised due to decomposition of the increasing urea in this population .Carbamylated plasma protein may influence the kidney directly , and has potential value in eval-uation of complications , prognosis , and therapy of chronic kidney disease patients .This review introduced plas-ma protein carbamylation and summarized its value as a biomarker in chronic kidney disease , and promising therapy focusing on lowering plasma protein carbamylation based on recent advances .

Carbamylation-induced inactivation of glyceraldehydes 3-phosphate dehydrogenase and thioltransferase in bovine lens / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate whether potassium cyanate can inactivate glyceraldehydes 3-phosphate dehydrogenase (GAPDH) and thioltransferase (TTase) in bovine lens.METHODS: Fresh intact bovine lenses were incubated with 100mmol/L potassium cyanate (KCNO) for 7 and 12 days respectively. Then all lens were incubated in 50mmol/L DMEM solution. The proteins in the watersoluble fractions from the normal control and the cyanate-modified lens were extracted. The activity of GAPDH and TTase in the water-soluble fraction after incubation at 37℃ was measured by spectrophotometer.RESULTS: GAPDH activity was significantly lower in the cyanate-modified lens proteins than that of the normal control (P<0.01), and considerably diminished in protein incubated with 100mmol/L potassium cyanate for 12 days. There were statistically significant differences in the activity of TTase between the normal control lenses and the carbamylated lenses incubated for 7 days (P<0.05) and 12 days (P<0.01). However. there was no statistical difference between the samples incubated with 100mmol/L KCNO for 7 and 12 days (P=0.19296).CONCLUSION: This study provides evidence to show carbamylation is able to inactivate GAPDH and TTase in bovine lenses. This may have implications for the susceptibility of lenticular GAPDH and TTase to carbamylation, and also for the research on pathogenesis of cataract.

Effect of Cyanate on the Carbamylation and Biological Activity of Superoxide Dismutase / 대한신장학회잡지

The patients with end stage renal disease show several complications such as artherosclerosis, anemia and increased susceptibility to infection by damage due to oxygen free radicals. Superoxide dismutase(SOD) is directly linked to the fate of the highly reactive oxygen metabolites. If there is an alteration in the activity of SOD, this alteration may contribute to the complications by reactive oxygen species in patients with end stage renal disease. In this experiment, SOD activity and the effect of cyanate on the activity of SOD was studied to understand the mechanism of several complications mediated by oxygen free radicals in patients with end stage renal disease. SOD activity in the plasma and erythrocytes from patients with end stage renal disease was significantly lower than those from healthy controls. It is known that underproduction of SOD leads to excess production of superoxide and reduced iron favoring hydroxyl radical formation. The results in this experiment suggest that there is an overproduction of superoxide anion in patients with end stage renal disease. The overproduction of superoxide anion may contribute the patients with end stage renal disease susceptible to oxidant damages. To evaluate if cyanate could carbamylate SOD, SOD was incubated with cyanate. The level of carbamylated SOD increased as the time of exposure to cyanate increased from 0 hour to 72 hours. Furthermore, the degree of carbamylation of SOD increased as cyanate concentration in the incubation media rose from 20mM to 1M. There appears to be a maximum degree of carbamylation at a concentration of 1,000mM cyanate. To test the hypothesis that in vitro carbamylation of SOD alters its biological activity, SOD activity was measured after incubation with cyanate. The activity of carbamylated SOD decreased as the time of exposure to cyanate increased from 0 hour to 72 hours. Furthermore, the activity of carbamylated SOD decreased as cyanate concentration in the incubation media rose from 20mM to 1M and when albumin was added to the reaction mixture, the loss of SOD activity was prevented. These results are consistent with the hypothesis that SOD is also carbamylated and lost biological activity in end stage renal disease patients by cyanate, and that the degree of carbamylation depends on both the concentration of cyanate and the length of exposure. Also, these suggest that albumin may prevent carbamylation of SOD at least in vitro condition.

Effect of Cyanate on Lens Protein Carbamylation and Catalase Activuty

Proteins are known to be carbamylated as a result of reactions with ureaderived cyanate. We investigated the effect of carbamylation by cyanate on the catalase activity which is known that its decreased activity contributes to cataract formation, and on the lens protein. Catalase and lens protein were carbamylated by incubation with cyanate at 37degrees C. The extent of carbamylation was monitored by following the loss of free amino group using trinitrobenzenesulphonic acid. The level of carbamylated protein was 76% in patients with cataract. Carbamylated proteins in normal lens from rabbits and carbamylated catalase were increased as the time of exposure to cyanate activity. Our results suggest that cyanate is an inhibitor of catalase, and carbamylation of catalase as a result of reaction with ureaderived cyanate may contribute to cataract formation.

Gramicidin-S: Structure–activity relationship.

The two side chain amino groups of the two L-ornithine residues in gramicidin-S seem to be important for the antibacterial activity of the molecule, since complete acetylation, formylation, carbamylation, deamination, trinitrophenylation, succinylation, maleylation of the antibiotic caused 90–95 % loss of the antibacterial activity of the antibiotic. However this modification leads to only 12–30% loss of the hemolytic activity. Monoacetyl- and monoformyl gramicidin-S with a free amino group retains nearly 50% of the antibacterial activity of the molecule. It seems, therefore, that the two amino groups contribute equally to the antibacterial activity of gramicidin-S.

Chemical modification of bacitracin A and the biological activity of modified bacitracins.

The single side chain amino group of the D-ornithine residue in bacitracin seems to be important for the antibacterial activity of the molecule, since, acetylation, formylation, carbamylation and deamination of the antibiotic caused 90-92% loss of antibacterial activity. In contrast, nearly 80-91% of the antibacterial activity of the parent antibiotic was retained after the esterification, amide formation and acid-chloride formation of the a - and Υ –carboxyl groups of D-asparagine and D-glutamic acid residues of the antibiotic, respectively.