Exendin-4 protects HUVECs from tunicamycin-induced apoptosis via inhibiting the IRE1a/JNK/caspase-3 pathway

Wu, Li; Li, Xiaoying; Wang, Lin-Xi; Wang, Yanping; Wang, Lijing; Guan, Binbin; Zhou, C.; Liu, Libin

doi:10.1007/s12020-016-1190-4

Cited by 14 publications

(9 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have demonstrated that GLP-1 has various protective effects on the endothelium. 23,[38][39][40] The results of our ex vivo experiments demonstrated that endothelial function was impaired by LPS in aortic segments isolated from wild-type mice, although Ex-4, a GLP-1 analog, ameliorated this response. Also, the results of our in vitro experiments using HUVEC demonstrated that Ex-4 ameliorated LPS-induced impairment of eNOS Ser1177 phosphorylation.…”

Section: Discussionmentioning

confidence: 76%

Vildagliptin, a DPP-4 Inhibitor, Attenuates Endothelial Dysfunction and Atherogenesis in Nondiabetic Apolipoprotein E-Deficient Mice

et al. 2019

View full text Add to dashboard Cite

Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel antidiabetic agents with possible vascular protection effects. Endothelial dysfunction is an initiation step in atherogenesis. The purpose of this study was to investigate whether vildagliptin (Vilda) attenuates the development of endothelial dysfunction and atherosclerotic lesions in nondiabetic apolipoprotein E-deficient (ApoE −/−) mice. Eight-week-old nondiabetic ApoE −/− mice fed a Westerntype diet received Vilda (50 mg/kg/day) for 20 weeks or 8 weeks. After 20 weeks of treatment, Vilda administration reduced atherogenesis in the aortic arch as determined by en face Sudan IV staining compared with the vehicle group (P < 0.05). Vilda also reduced lipid accumulation (P < 0.05) and vascular cell adhesion molecule-1 (VCAM-1) expression (P < 0.05) and tended to decrease macrophage infiltration (P = 0.05) into atherosclerotic plaques compared with vehicle. After 8 weeks of treatment, endothelium-dependent vascular reactivity was examined. Vilda administration significantly attenuated the impairment of endothelial function in nondiabetic ApoE −/− mice compared with the vehicle group (P < 0.05). Vilda treatment did not alter metabolic parameters, including blood glucose level, in both study protocols. To investigate the mechanism, aortic segments obtained from wild-type mice were incubated with exendin-4 (Ex-4), a glucagon-like peptide-1 (GLP-1) analog, in the presence or absence of lipopolysaccharide (LPS). Ex-4 attenuated the impairment of endothelium-dependent vasodilation induced by LPS (P < 0.01). Furthermore, Ex-4 promoted phosphorylation of eNOS at Ser1177 which was decreased by LPS in human umbilical endothelial cells (P < 0.05). Vilda inhibited the development of endothelial dysfunction and prevented atherogenesis in nondiabetic ApoE −/− mice. Our results suggested that GLP-1-dependent amelioration of endothelial dysfunction is associated with the atheroprotective effects of Vilda.

show abstract

Section: Discussionmentioning

confidence: 76%

Vildagliptin, a DPP-4 Inhibitor, Attenuates Endothelial Dysfunction and Atherogenesis in Nondiabetic Apolipoprotein E-Deficient Mice

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In addition, we found that autophagy deficiency in IECs was accompanied by an enhancement of JNK activation and apoptosis of colonic epithelial cells. Since excessive ER stress has been reported to induce apoptosis via the IRE1a-JNK pathway in various cell types, (44) these findings suggest that autophagy in IECs suppresses epithelial apoptosis via inhibition of the IRE1a-JNK pathway leading to protection against chronic colitis.…”

Section: Discussionmentioning

confidence: 94%

Targeted deletion of Atg5 in intestinal epithelial cells promotes dextran sodium sulfate-induced colitis

Nishino

Nishida

Inatomi

et al. 2021

J. Clin. Biochem. Nutr.

View full text Add to dashboard Cite

Autophagy associated genes have been identified as susceptible loci for inflammatory bowel disease. We investigated the role of a core autophagy factor, Atg5, in the development of dextran sodium sulfate (DSS) induced colitis. Intestinal epithelial cell (IEC) specific Atg5 gene deficient mice (Atg5 ΔIEC mice) were generated by cross of Atg5 floxed mice (Atg5 fl/fl) with transgenic mice expressing Cre recombinase driven by the villin promotor. Mice were given three cycles of 1.5% DSS in drinking water for 5 days and regular water for 14 days over a 60 day period. The dysfunc tion of autophagy characterized by a marked accumulation of p62 protein, a substrate for autophagy degradation, was detected in epithelial cells in the non inflamed and inflamed mucosa of inflammatory bowel disease patients. DSS colitis was exacerbated in Atg5 ΔIEC mice compared to control Atg5 fl/fl mice. Phosphorylation of inositol requiring transmembrane kinase/endonuclease1α (IRE1α), a sensor for endoplasmic reticulum stress, and c Jun N terminal kinase, a downstream target of IRE1α, were significantly enhanced in IECs in DSS treated Atg5 ΔIEC mice. Accumulation of phosphorylated IRE1α was enhanced by the treatment with chloroquine, an autophagy inhibitor. Apoptotic IECs were more abundant in DSS treated Atg5 ΔIEC mice. These findings suggest that Atg5 suppresses endoplasmic reticulum stress induced apoptosis of IECs via the degradation of excess p IRE1α.

show abstract

“…Downregulation of JUN can signi cantly reduce the expression of in ammatory factors and inhibit endothelial cell apoptosis. 39 Tumor necrosis factor (TNF) is a multifunctional cytokine that can directly damage islet -cells and induce insulin resistance by inhibiting the transduction of insulin signals. MAPK is a serine/threonine protein kinase involved in cell proliferation, differentiation, apoptosis, and in ammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Quercetin Therapeutic Targets for Alzheimer Disease and type 2 Diabetes Mellitus

Sun

et al. 2021

Preprint

View full text Add to dashboard Cite

Quercetin has demonstrated antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic activities, suggesting therapeutic potential against type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). In this study, potential molecular targets of quercetin were first identified using the Swiss Target Prediction platform and pathogenic targets of T2DM and AD were identified using Online Mendelian Inheritance in Man (OMIM), DisGeNET, TTD, DrugBank, and GeneCards databases. The 95 targets shared among quercetin, T2DM, and AD were used to establish a protein–protein interaction (PPI) network, top 25 core genes, and protein functional modules using MCODE. Metascape was then used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A protein functional module with best score was obtained from the PPI network using CytoHubba, and 6 high-probability quercetin targets (AKT1, JUN, MAPK, TNF, VEGFA, and EGFR) were confirmed by docking simulations. KEGG pathway enrichment analysis suggested that the major shared mechanisms for T2DM and AD include “AGE-RAGE signaling pathway in diabetic complications,” “pathways in cancer,” and “MAPK signaling pathway” (the key pathway). We speculate that quercetin may have therapeutic applications in T2DM and AD by targeting MAPK signaling, providing a theoretical foundation for future clinical research.

show abstract

Exendin-4 protects HUVECs from tunicamycin-induced apoptosis via inhibiting the IRE1a/JNK/caspase-3 pathway

Abstract: This study demonstrates that Exendin-4 can protect human umbilical vein endothelial cells from tunicamycin-induced apoptosis. Furthermore, our data suggests that the mechanism for this effect is mediated by inhibiting the IRE1α/JNK/caspase-3 pathway.

Cited by 14 publications

References 31 publications

Vildagliptin, a DPP-4 Inhibitor, Attenuates Endothelial Dysfunction and Atherogenesis in Nondiabetic Apolipoprotein E-Deficient Mice

Vildagliptin, a DPP-4 Inhibitor, Attenuates Endothelial Dysfunction and Atherogenesis in Nondiabetic Apolipoprotein E-Deficient Mice

Targeted deletion of Atg5 in intestinal epithelial cells promotes dextran sodium sulfate-induced colitis

Mechanism of Quercetin Therapeutic Targets for Alzheimer Disease and type 2 Diabetes Mellitus

Contact Info

Product

Resources

About