GLP-1 treatment protects endothelial cells from oxidative stress-induced autophagy and endothelial dysfunction

Cai, Xiangsheng; She, Miaoqin; Xu, Mingyu; Chen, Huiying; Li, Jingjing; Chen, Xinglu; Zheng, Dandan; Li, Jun; Chen, Shangliang; Zhu, Jianbin; Xu, Xiaosong; Li, Ruiying; Li, Jinlong; Chen, Shaolian; Yang, Xiaorong; Li, Hongwei

doi:10.7150/ijbs.27774

Cited by 58 publications

(40 citation statements)

References 45 publications

(43 reference statements)

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“…In this study, we used PA to establish endothelial oxidative stress model to simulate the high saturated fatty acid diet in AS. In the most previous studies of the antioxidant effects of RSV, oxidative stress model is established by H 2 O 2 , which is a type of direct exogenous ROS [41–44]. However, although RSV can directly scavenge ROS in vitro, its antioxidant properties in vivo are more likely to be attributed to its effects as a gene regulator [34].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol attenuates oxidative injury in human umbilical vein endothelial cells through regulating mitochondrial fusion via TyrRS-PARP1 pathway

et al. 2019

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Background/aimsOxidative stress-induced damage in endothelial cells is a crucial initiator of atherosclerosis (AS), which is highly related to excessive reactive oxygen species (ROS) and mitochondrial dynamics. Resveratrol (RSV) exerts beneficial effects against endothelial oxidative injury, while the underlying mechanisms have not been fully elucidated. Thus, we aimed to explore the role of mitochondria dynamics during the anti-oxidative activities of RSV in palmitic acid (PA)-stimulated human umbilical vein endothelial cells (HUVECs) and to verify whether tyrosyl transfer- RNA synthetase (TyrRS) and poly (ADP-ribose) polymerase 1 (PARP1) are targeted during this process.MethodsHUVECs were exposed to 200 μM of PA for 16 h before treated with 10 μM of RSV for 8 h. Cell viability was detected using Cell counting kit-8 (CCK-8) assay. The intracellular ROS level and mitochondria membrane potential (MMP) were measured using microplate reader and flow cytometry. The malondialdehyde and superoxide dismutase were measured using the microplate reader. The mitochondrial morphology and fusion process was observed under transmission electron microscopy and confocal microscopy. TyrRS and PARP1 were knocked down with the specific small interference RNAs (siRNA), and the protein expressions of TyrRS, PARP1, and mitochondrial fusion proteins (MFN1, MFN2, and OPA1) were measured by western blot.ResultsRSV treatment suppressed the PA-induced injuries in HUVECs, including the damage to cell viability, oxidative stress, and loss of MMP. Additionally, RSV improved the protein levels of MFN1, MFN2, and OPA1 as well as inhibited the PA-induced fragmentation of mitochondria. However, the effects of RSV on oxidative stress and mitochondrial fusion were abolished by the pretreatment of siRNAs of TyrRS and PARP1, indicating that these effects of RSV were dependent on the TyrRS-PARP1 pathway.ConclusionsRSV attenuated endothelial oxidative injury by regulating mitochondrial fusion via TyrRS-PARP1 signaling pathway.Electronic supplementary materialThe online version of this article (10.1186/s12986-019-0338-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Resveratrol attenuates oxidative injury in human umbilical vein endothelial cells through regulating mitochondrial fusion via TyrRS-PARP1 pathway

et al. 2019

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“…GLP-1 has also been shown to have an extra-pancreatic effect that inhibits gastric emptying and reduces food intake [16,17]. GLP-1 receptor agonists have been studied in recent years on cardiovascular disease and endothelial dysfunction [18], and its treatment protects endothelial cells from oxidative stress-induced autophagy and endothelial dysfunction [19]. Liraglutide suppressing endothelin-1 (ET-1) and enhancing endothelium NO synthase (eNOS)/soluble guanylate cyclase (sGC)/protein kinase G (PKG) pathways were also studied in animal models of monocrotaline-induced PAH [20].…”

Section: Introductionmentioning

confidence: 99%

Glucagon-Like Peptide-1 Receptor Agonist Attenuates Autophagy to Ameliorate Pulmonary Arterial Hypertension through Drp1/NOX- and Atg-5/Atg-7/Beclin-1/LC3β Pathways

Wang

Lee

et al. 2019

IJMS

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Mitochondrial dysfunction is associated with cardiovascular diseases and diabetes. Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling, and the abnormal proliferation, apoptosis and migration of pulmonary arterial smooth muscle cells (PASMCs). The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, has been shown to prevent pulmonary hypertension in monocrotaline-exposed rats. The aim of this study was to investigate the effect of liraglutide on autophagy, mitochondrial stress and apoptosis induced by platelet-derived growth factor BB (PDGF-BB). PASMCs were exposed to PDGF-BB, and changes in mitochondrial morphology, fusion-associated protein markers, and reactive oxygen species (ROS) production were examined. Autophagy was assessed according to the expressions of microtubule-associated protein light chain 3 (LC3)-II, LC3 puncta and Beclin-1. Western blot analysis was used to assess apoptosis, mitochondrial stress and autophagy markers. Liraglutide significantly inhibited PDGF-BB proliferation, migration and motility in PASMCs. PDGF-BB-induced ROS production was mitigated by liraglutide. Liraglutide increased the expression of α-smooth muscle actin (α-SMA) and decreased the expression of p-Yes-associated protein (p-YAP), inhibited autophagy-related protein (Atg)-5, Atg-7, Beclin-1 and the formation of LC3-β and mitochondrial fusion protein dynamin-related (Drp)1. Therefore, liraglutide can mitigate the proliferation of PASMCs via inhibiting cellular Drp1/nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) pathways and Atg-5/Atg-7/Beclin-1/LC3β-dependent pathways of autophagy in PAH.

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“…It has also been reported that DPP-4 inhibitors decreased oxidative stress and inflammation in the kidney after cisplatin administration in animal models [4,5]. In addition, it has been reported that GLP-1 receptor agonists reduced oxidative stress and inflammation in the kidney in ischemia-reperfusion injury, and protected endothelial cells from oxidative stress-induced injury [32,33].…”

Section: Discussionmentioning

confidence: 94%

Effect of dipeptidyl peptidase-4 inhibitors on cisplatin-induced acute nephrotoxicity in cancer patients with diabetes mellitus: A retrospective study

et al. 2020

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Background Cisplatin is a highly effective chemotherapeutic agent. However, acute kidney injury (AKI) limits its subsequent use, resulting in poor cancer prognosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to attenuate cisplatin-induced AKI in animal models, but the effect in human patients remains to be clarified. We hypothesized that DPP-4 inhibitors can prevent cisplatin-induced AKI in diabetic-cancer patients. Methods We retrospectively reviewed all consecutive cancer patients who were treated with a first cycle of cisplatin-containing regimen between January 2011 and October 2019. We analysed data of diabetic-cancer patients treated with high-dose cisplatin (> 50 mg/m 2)-containing regimens. The change of estimated glomerular filtration rate (eGFR) within 2 weeks after cisplatin treatment was compared between the patients treated with DPP-4 inhibitors and those treated without DPP-4 inhibitors. Results A total of 455 patients were treated with cisplatin during the period. Of these, 34 patients were eligible for the analysis. The change of eGFR was significantly less in the patients treated with DPP-4 inhibitors, compared to those without DPP-4 inhibitors [the percentages of eGFR decline (mean ± SD) was 23.6 ± 20.3% vs 43.1± 20.1%, respectively; P = 0.010]. Furthermore, the incidence of AKI was significantly less in the patients treated with DPP-4 inhibitors (25% vs 64%, respectively; P = 0.026). Conclusions DPP-4 inhibitors may decrease the risk of cisplatin-induced AKI in diabetic patients.

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GLP-1 treatment protects endothelial cells from oxidative stress-induced autophagy and endothelial dysfunction

Cited by 58 publications

References 45 publications

Resveratrol attenuates oxidative injury in human umbilical vein endothelial cells through regulating mitochondrial fusion via TyrRS-PARP1 pathway

Resveratrol attenuates oxidative injury in human umbilical vein endothelial cells through regulating mitochondrial fusion via TyrRS-PARP1 pathway

Glucagon-Like Peptide-1 Receptor Agonist Attenuates Autophagy to Ameliorate Pulmonary Arterial Hypertension through Drp1/NOX- and Atg-5/Atg-7/Beclin-1/LC3β Pathways

Effect of dipeptidyl peptidase-4 inhibitors on cisplatin-induced acute nephrotoxicity in cancer patients with diabetes mellitus: A retrospective study

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