ABSTRACT
This study investigated the effect of angiotensin II (Ang II) on apoptosis and thioredoxin-interacting protein (TXNIP) expression in INS-1 islet cells and the underlying mechanism. INS-1 cells cultured in vitro were treated with different concentration of Ang II for different time, and the viability was measured using cell counting kit-8 (CCK-8). After treatment with 1 × 10 mol/L Ang II for 24 h, flow cytometry and Western blot were used to measure the cell apoptosis, and Western blot was used to analyze the protein expression of TXNIP, carbohydrate response element-binding protein (ChREBP) and angiotensin II type 1 receptor (AT1R). Real-time PCR was used to detect TXNIP and ChREBP mRNA expression. IF/ICC was used to observe the TXNIP, ChREBP and AT1R expression. The results showed that Ang II reduced cell viability and induced the expression of TXNIP in a dose- and time-dependent manner (P < 0.05, n = 6) compared with the control group. Ang II induced apoptosis and up-regulated the expression of ChREBP and AT1R (P < 0.05, n = 6). AT1R inhibitor, telmisartan (TM), blocked Ang II-induced TXNIP and ChREBP overexpression (P < 0.05, n = 6) and inhibited Ang II-induced apoptosis. Taken together, Ang II increased ChREBP activation through AT1R, which subsequently increased TXNIP expression and promoted cell apoptosis. These findings suggest a therapeutic potential of targeting TXNIP in preventing Ang II-induced INS-1 cell apoptosis in diabetes.
ABSTRACT
Diabetes can cause a significant increase in the expression of thioredoxin (Trx)-interacting protein (TXNIP), which binds to Trx and inhibits its activity. The present study was aimed to investigate the effect of TXNIP on proliferation of rat INS-1 islet β cells and the underlying mechanism. TXNIP overexpressing adenovirus vectors (Ad-TXNIP-GFP and Ad-TXNIPc247s-GFP) were constructed and used to infect INS-1 cells. Ad-TXNIPc247s-GFP vector carries a mutant C247S TXNIP gene, and its expression product (TXNIPc247s) cannot attach and inhibit Trx activity. The expression of TXNIP was detected by real-time PCR and Western blot. EdU and Ki67 methods were used to detect cell proliferation. Protein phosphorylation levels of ERK and AKT were detected by Western blot. The results showed that both TXNIP and TXNIPc247s protein overexpressions inhibited the proliferation of INS-1 cells, and the former's inhibitory effect was greater. Moreover, both of the two kinds of overexpressions inhibited the phosphorylation of ERK and AKT. These results suggest that TXNIP overexpression may inhibit the proliferation of INS-1 cells through Trx-dependent and non-Trx-dependent pathways, and the mechanism involves the inhibition of ERK and AKT phosphorylation.
ABSTRACT
Objective To detect the damage of hippocampal neurons and the changes in inflammatory cytokines in rats after cerebral ischemia-reperfusion(I/R)and compare the expressions of IL-1β,IL-6 and TNFαin hippocampal DG,CA1 and CA3 subregions.Methods The focal cerebral I/R model was induced by an intraluminal filament embolism.The SD rats were randomly divided into the sham-operated group(SHAM group)and the middle cerebral artery occlusion-reperfusion group(MCAO group).HE staining was employed to detect the damage to hippocampal DG, CA1 and CA3 subregions.The expression levels of IL-1β, IL-6 and TNFα were detected by immunofluorescence assay.Results Compared with SHAM group,hippocampal DG,CA1 and CA3 subregion neurons in MCAO group were severely damaged, with occurred inflammatory cell infiltration,and a large amount of neurons apoptosis, and the expressions of IL-1β, IL-6 and TNFαin each subregion increased significantly.At the same time, in MCAO group, the expression of inflammatory cytokines in CA1 subregion was more significant than that in DG and CA 3 subregions(P<0.05).Conclusion Cerebral I/R could cause neuronal damage, inflammatory cell infiltration, and neuronal apoptosis in the DG, CA1 and CA3 subregions of the hippocampus and increase the release of inflammatory cytokines.In MCAO group, the expression of inflammatory cytokines in CA1 subregion of hippocampus is significantly higher than that in DG and CA 3 subregions, suggesting that CA1 region is more sensitive to I/R injury.
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Objective The aim of this study was to systematically evaluate the health status of Asian immigrants in Canada and the associated factors. Methods Using data from the 2003 Canadian Community Health Survey, a descriptive analysis was performed to estimate the frequency of health associated factors among different populations. Age-standardization rates was also used to compare the prevalence of chronic conditions among Asian immigrants, other immigrants and native residents. Logistic regression analysis was used to estimate the adjusted Odds ratio (0R) associated with each health outcome and 95% confidence interval (95%CI) after controlling for potential confounding factors. Results After age-standardization, Asian immigrants had a similar prevalence of 1-5 chronic conditions and a lower prevalence of 5+ chronic conditions (3.56%) compared with non-immigrants (5.31%). Asian immigrants were less likely to report any chronic disease (0R=0.49, 95% CI: 0.46-0.51) than non- immigrants (0R=1.00). Recent Asian immigrants were less likely to report any chronic condition (0R=0.34, 95% CI: 0.31-0.37) than long-term Asian immigrants (0R=0.62, 95% VI: 0.58-0.66). After adjusting for socioeconomic status and lifestyle factors, Asian immigrants had a slightly changed risk of four chronic conditions with exception of heart disease. Conclusion Asian immigrants had lower risk of chronic conditions as a whole, however, these health advantages decreased along with increasing length of residence in Canada. Socioeconomic factors and lifestyles cannot fully explain the differences of health status between Asian immigrants and non-immigrant Canadians reported in this paper.
ABSTRACT
<p><b>OBJECTIVES</b>To investigate the effect of selective cyclooxygenase-2 (COX-2) inhibitor on alcohol-induced liver injury in rats.</p><p><b>METHODS</b>58 male Wistar rats were randomly divided into three groups: control group treated with dextrose and corn oil, model group with ethanol and corn oil, treatment group with corn oil and ethanol plus a selective COX-2 inhibitor celecoxib. All treatments were injected into stomach through intragastric tubes. Liver samples were analyzed for histopathology with light microscope (LM) and transmission electron microscope (TEM), and the expression of COX-2 with western blotting. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, levels of 6-Keto-prostaglandin F1 alpha (6-k-PGF1a) and thromboxane B2 (TXB2) in liver, and activity of glutathione s-transferase (GST) both in liver tissue and in plasma were measured.</p><p><b>RESULTS</b>LM and TEM indicated hepatocytes were injured obviously in the model group and slightly in the treatment group. The levels of AST and ALT in serum, TXB2 in liver and the activity of GST in plasma increased significantly in the model group (t> or =2.294, P<0.05), but the activity of GST in liver decreased significantly (t=8.856, P<0.01) compared with those in the control group. To compare with the model group, the levels of AST and TXB2 decreased significantly (t=4.305, P<0.01; t=2.799, P<0.01), meanwhile the activity of GST increased significantly (t=10.134, P<0.01) in the treatment group. COX-2 expression in liver by western blotting increased significantly in the model group, compared with the control group (t=4.067, P<0.01) and the treatment group (t=2.251, P<0.05). Exceptionally, the level of 6-k-PGF1a decreased significantly (t=2.284, P<0.05) in the model group.</p><p><b>CONCLUSION</b>COX-2 has involved in the alcohol-induced liver injury, and its inhibitor can diminish alcohol-induced liver injury in rats through decreasing TXB2 level</p>