Proteome-Wide Analysis of Single-Nucleotide Variations in the N-Glycosylation Sequon of Human Genes

N-linked glycosylation is one of the most frequent post-translational modifications of proteins with a profound impact on their biological function. Besides other functions, N-linked glycosylation assists in protein folding, determines protein orientation at the cell surface, or protects proteins from proteases. The N-linked glycans attach to asparagines in the sequence context Asn-X-Ser/Thr, where X is any amino acid except proline. Any variation (e.g. non-synonymous single nucleotide polymorphism or mutation) that abolishes the N-glycosylation sequence motif will lead to the loss of a glycosylation site. On the other hand, variations causing a substitution that creates a new N-glycosylation sequence motif can result in the gain of glycosylation. Although the general importance of glycosylation is well known and acknowledged, the effect of variation on the actual glycoproteome of an organism is still mostly unknown. In this study, we focus on a comprehensive analysis of non-synonymous single nucleotide variations (nsSNV) that lead to either loss or gain of the N-glycosylation motif. We find that 1091 proteins have modified N-glycosylation sequons due to nsSNVs in the genome. Based on analysis of proteins that have a solved 3D structure at the site of variation, we find that 48% of the variations that lead to changes in glycosylation sites occur at the loop and bend regions of the proteins. Pathway and function enrichment analysis show that a significant number of proteins that gained or lost the glycosylation motif are involved in kinase activity, immune response, and blood coagulation. A structure-function analysis of a blood coagulation protein, antithrombin III and a protease, cathepsin D, showcases how a comprehensive study followed by structural analysis can help better understand the functional impact of the nsSNVs

Relationship between serum concentrations of interleukin-6 and tumor necrosis factor alpha in female Turkish subjects with normal and impaired glucose tolerance

Serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF alpha) concentrations were measured in subjects during two-hour glucose loading in order to investigate the effects of glucose on serum IL-6 and TNFa concentrations. Twenty-six female subjects (mean age 60 10 years) had normal glucose tolerance (NGT) and nineteen female subjects (mean age: 63 9 years) had impaired glucose tolerance (IGT) according to WHO criteria. Serum IL-6 and TNF alpha concentrations were measured by chemiluminescent immunometric assay. Subjects with IGT have higher fasting serum TNF alpha levels than subjects with NGT (p < 0.01). Serum IL-6 and TNFa concentrations were elevated during glucose loading (for each comparision, p < 0.01). The increase in serum TNF alpha concentrations in IGT was greater than in NGT (p < 0.01). Serum IL-6 and TNF alpha concentration significantly correlated with insulin and glucose in IGT group (for each comparision, p < 0.01). The correlation between serum glucose and cytokines concentrations was significant in IGT (for each comparision, p < 0.01). There was also a positive correlation between serum IL-6 and TNFa in NGT and IGT (for each comparision, p < 0.01). In conclusion, hyperglycemia is associated with increased circulating cytokine concentrations and fasting TNF alpha concentrations seem to be more associated with IGT than IL-6

Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients by transient intensive insulin treatment

OBJECTIVE - Type 2 diabetes is a slowly progressive disease, in which the gradual deterioration of glucose tolerance is associated with the progressive decrease in beta-cell function. Hyperglycemia per se has deleterious effects on both beta-cell function and insulin action, which are partially reversible by the short-term control of blood glucose levels. We hypothesized that the induction of euglycemia, using intensive insulin therapy at the time of clinical diagnosis, could lead to a significant improvement in insulin secretion and action and thus alter the clinical course of the disease

High prevalence of obesity and diabetes mellitus in Konya, a central Anatolian city in Turkey

Introduction: The objective of this study was to determine the prevalence of overweight, obesity, impaired fasting glucose, diabetes and the relationship between adiposity and carbohydrate metabolism, by age and gender in Konya, a city in central Anatolia

The effects of epidural bupivacaine on ischemia/reperfusion-induced liver injury

BACKGROUND: Several animal studies showed beneficial effects of thoracic epidural anesthesia (TEA) in hippocampal, mesenteric and myocardial IR injury (2-4). In this study, we investigated the effects of epidural bupivacaine on hepatic ischemia reperfusion injury in a rat model. MATERIAL AND METHODS: Eighteen rats were randomly divided into three groups each containing 6 animals. The rats in Group C had sham laparotomy. The rats in the Group S were subjected to liver IR through laparotomy and 20 mcg/kg/h 0.9 \% NaCl was administered to these rats via an epidural catheter. The rats in the Group B were subjected to liver IR and were given 20 mcg/kg/h bupivacaine via an epidural catheter. Liver tissue was harvested for MDA analysis, apoptosis and histopathological examination after 60 minutes of ischemia followed by 360 minutes of reperfusion. Blood samples were also collected for TNF-alpha, IL-1 beta, AST and ALT analysis. RESULTS: The AST and ALT levels were higher in ischemia and reperfusion group, which received only normal saline via the thoracic epidural catheter, compared to the sham group. In the ischemia reperfusion group, which received bupivacaine via the epidural catheter, IL-1 levels were significantly higher than in the other groups. TNF-a levels were higher in the Groups S and B compared to the sham group. Bupivacaine administration induced apoptosis in all animals. CONCLUSION: These results showed that thoracic epidural bupivacaine was not a suitable agent for preventing inflammatory response and lipid peroxidation in experimental hepatic IR injury in rats. Moreover, epidural bupivacaine triggered apoptosis in hepatocytes. Further research is needed as there are no studies in literature investigate the effects of epidural bupivacaine on hepatic ischemia reperfusion injury (Tab. 3, Fig. 3, Ref. 34). Text in PDF www.elis.sk