Journal of Shandong University (Health Sciences) ›› 2023, Vol. 61 ›› Issue (8): 10-16.doi: 10.6040/j.issn.1671-7554.0.2023.0450

• 基础医学 • Previous Articles    

GLP-1 inhibits oxidative stress damage through cytochrome P450 surface oxidase pathway

HU Yanwen1, ZHAO Huichen2, MA Xiaoli2, LIU Yuantao3, ZHANG Yuchao2   

  1. 1. Department of Nutrition, Heze Municipal Hospital, Heze 274000, Shandong, China;
    2. Department of Endocrinology, Qingdao Municipal Hospital, Qingdao 266011, Shandong, China;
    3. Department of Endocrinology, Qilu Hospital(Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, Shandong, China
  • Published:2023-08-30

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Abstract: Objective To explore the effects of GLP-1 against oxidative stress in vitro and the possible mechanism from cytochrome P450(CYP450)epoxygenase pathway. Methods Human umbilical vein endothelial cells(HUVECs)were treated with H2O2 to construct the oxidative stress models. The cells were divided into six groups: control group, H2O2 group, H2O2+7-36a group, H2O2+9-36a group, H2O2+7-36a+Danazol group and H2O2+9-36a+Danazol group. Cell viability was evaluated with CCK8 assay. Intracellular ROS level was determined with fluorescent probe labeling. The expressions of glucose regulatory protein 78(GRP78)and cytochrome P450 2J2(CYP2J2)were detected with Western blotting. Results Oxidative stress models were constructed after 600 μmol/L H2O2 treatment for 3 hours. Compared with the control group, the H2O2 group had decreased cell survival rate(P<0.001), increased ROS level(P<0.001)and protein expression of GRP78(P<0.05), but decreased CYP2J2 protein expression(P<0.05). Compared with the H2O2 group, the H2O2+7-36a group and H2O2+9-36a group had increased survival rate(P<0.05, P<0.01), decreased ROS level(both P<0.001)and GRP78 protein expression(both P<0.01), and increased CYP2J2 protein expression(both P<0.05). Compared with the H2O2+7-36a group, there was no statistical difference in cell survival rate in the H2O2+7-36a+Danazol group, while the ROS level increased(P<0.001), GRP protein expression incresed(P<0.001), and CYP2J2 protein expression decreased(P<0.05). Compared with the H2O2+9-36a group, there was no statistical difference in cell survival rate in the H2O2+9-36a+Danazol group, while the ROS level increased(P<0.001), GRP protein expression incresed(P<0.01), and CYP2J2 protein expression decreased(P<0.01). Conclusion GLP-1(7-36a)and its metabolite GLP-1(9-36a)can improve H2O2-induced survival decline in HUVECs and reduce the high level of oxidative stress, possibly through the CYP450 epoxygenase pathway.

Key words: Human umbilical vein endothelial cells, Oxidative stress, GLP-1, Cytochrome P450

CLC Number: 

  • R589
[1] Low Wang CC, Hess CN, Hiatt WR, et al. Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus-mechanisms, management, and clinical considerations[J]. Circulation, 2016, 133(24): 2459-2502.
[2] Zimmet PZ. Diabetes and its drivers: the largest epidemic in human history?[J]. Clin Diabetes Endocrinol, 2017, 3: 1. doi:10.1186/s40842-016-0039-3.
[3] Batchuluun B, Inoguchi T, Sonoda N, et al. Metformin and liraglutide ameliorate high glucose-induced oxidative stress via inhibition of PKC-NAD(P)H oxidase pathway in human aortic endothelial cells[J]. Atherosclerosis, 2014, 232(1): 156-164.
[4] Takahashi P, Xavier DJ, Lima JEBF, et al. Transcript expression profiles and microRNA regulation indicate an upregulation of processes linked to oxidative stress, DNA repair, cell death, and inflammation in type 1 diabetes mellitus patients[J]. J Diabetes Res, 2022, 2022:3511329. doi: 10.1155/2022/3511329.
[5] Li JF, Zheng J, Wang S, et al. Cardiovascular benefits of native GLP-1 and its metabolites: an indicator for GLP-1-therapy strategies[J]. FrontPhysiol, 2017, 8: 15. doi:10.3389/fphys.2017.00015.
[6] Al-Dwairi A, Alqudah TE, Al-Shboul O, et al. Glucagon-like peptide-1 exerts anti-inflammatory effects on mouse colon smooth muscle cells through the cyclic adenosine monophosphate/nuclear factor-κB pathway in vitro[J]. Inflamm Res, 2018, 11: 95-109. doi: 10.2147/JIR.S152835.
[7] Wang DJ, Luo P, Wang YB, et al. Glucagon-like peptide-1 protects against cardiac microvascular injury in diabetes via a cAMP/PKA/Rho-dependent mechanism[J]. Diabetes, 2013, 62(5): 1697-1708.
[8] Shen M, Sun DD, Li WJ, et al. The synergistic effect of valsartan and LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo] acetyl-2-cyanopyrrolidine] on vascular oxidative stress and inflammation in type 2 diabetic mice[J]. Exp Diabetes Res, 2012, 2012: 146194. doi:10.1155/2012/146194.
[9] Zhang SS, Chen GZ, Li N, et al. CYP2J2 overexpression ameliorates hyperlipidemia via increased fatty acid oxidation mediated by the AMPK pathway[J]. Obesity, 2015, 23(7): 1401-1413.
[10] Aliwarga T, Evangelista EA, Sotoodehnia N, et al. Regulation of CYP2J2 and EET levels in cardiac disease and diabetes[J]. Int J Mol Sci, 2018, 19(7): 1916. doi:10.3390/ijms19071916.
[11] Wang Y, Wei X, Xiao X, et al. Arachidonic acid epoxygenase metabolites stimulate endothelial cell growth and angiogenesis via mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signaling pathways[J]. J Pharmacol Exp Ther, 2005, 314(2): 522-532.
[12] Yang SL, Lin L, Chen JX, et al. Cytochrome P-450 epoxygenases protect endothelial cells from apoptosis induced by tumor necrosis factor-alpha via MAPK and PI3K/Akt signaling pathways[J]. Am J Physiol Heart Circ Physiol, 2007, 293(1): H142-H151.
[13] Chen GZ, Wang PH, Zhao G, et al. Cytochrome P450 epoxygenase CYP2J2 attenuates nephropathy in streptozotocin-induced diabetic mice[J]. Prostaglandins Other Lipid Mediat, 2011, 96(1/2/3/4): 63-71.
[14] Xu XZ, Zhao CX, Wang LY, et al. Increased CYP2J3 expression reduces insulin resistance in fructose-treated rats and db/db mice[J]. Diabetes, 2010, 59(4): 997-1005.
[15] Abraham NG, Sodhi K, Silvis AM, et al. CYP2J2 targeting to endothelial cells attenuates adiposity and vascular dysfunction in mice fed a high-fat diet by reprogramming adipocyte phenotype[J]. Hypertension, 2014, 64(6): 1352-1361.
[16] Dal Canto E, Ceriello A, Rydén L, et al. Diabetes as a cardiovascular risk factor: an overview of global trends of macro and micro vascular complications[J]. Eur J Prev Cardiol, 2019, 26(2_suppl): 25-32.
[17] Chen G, Cai LC, Chen B, et al. Serum level of endogenous secretory receptor for advanced glycation end products and other factors in type 2 diabetic patients with mild cognitive impairment[J]. Diabetes Care, 2011, 34(12): 2586-2590.
[18] Weyemi U, Dupuy C. The emerging role of ROS-generating NADPH oxidase NOX4 in DNA-damage responses[J]. Mutat Res, 2012, 751(2): 77-81.
[19] Leon BM, Maddox TM. Diabetes and cardiovascular disease: epidemiology, biological mechanisms, treatment recommendations and future research[J]. World J Diabetes, 2015, 6(13): 1246-1258.
[20] Li Q, Lin YJ, Wang S, et al. GLP-1 inhibits high-glucose-induced oxidative injury of vascular endothelial cells[J]. Sci Rep, 2017, 7(1): 8008. doi:10.1038/s41598-017-06712-z.
[21] Boudreau HE, Casterline BW, Burke DJ, et al. Wild-type and mutant p53 differentially regulate NADPH oxidase 4 in TGF-β-mediated migration of human lung and breast epithelial cells[J]. Br J Cancer, 2014, 110(10): 2569-2582.
[22] Shah HS, Morieri ML, Marcovina SM, et al. Modulation of GLP-1 levels by a genetic variant that regulates the cardiovascular effects of intensive glycemic control in ACCORD[J]. Diabetes Care, 2018, 41(2): 348-355.
[23] Yue W, Li Y, Ou DK, et al. The GLP-1 receptor agonist liraglutide protects against oxidized LDL-induced endothelial inflammation and dysfunction via KLF2[J]. IUBMB Life, 2019, 71(9): 1347-1354.
[24] Gaspari T, Liu HB, Welungoda I, et al. A GLP-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an ApoE-/- mouse model[J]. Diab Vasc Dis Res, 2011, 8(2): 117-124.
[25] Cheng CK, Luo JY, Lau CW, et al. A GLP-1 analog lowers ER stress and enhances protein folding to ameliorate homocysteine-induced endothelial dysfunction[J]. Acta Pharmacol Sin, 2021, 42(10): 1598-1609.
[26] Lu SC. Antioxidants in the treatment of chronic liver diseases: why is the efficacy evidence so weak in humans?[J]. Hepatology, 2008, 48(5): 1359-1361.
[27] Eid S, Abou-Kheir W, Sabra R, et al. Involvement of renal cytochromes P450 and arachidonic acid metabolites in diabetic nephropathy[J]. J Biol Regul Homeost Agents, 2013, 27(3): 693-703.
[28] Li NN, Zhao YH, Yue YY, et al. Liraglutide ameliorates palmitate-induced endothelial dysfunction through activating AMPK and reversing leptin resistance[J]. Biochem Biophys Res Commun, 2016, 478(1): 46-52.
[29] Dannawi M, Riachi ME, Haddad AF, et al. Influence of intermittent fasting on prediabetes-induced neuropathy: insights on a novel mechanistic pathway[J]. Metabol Open, 2022, 14: 100175. doi:10.1016/j.metop.2022.100175.
[30] Njeim R, Braych K, Ghadieh HE, et al. VEGF-A: anovel mechanistic link between CYP2C-derived EETs and Nox4 in diabetic kidney disease[J]. Diabetes, 2023, 72(7): 947-957.
[31] Guo K, Ge J, Zhang C, et al. `Cadmium induced cardiac inflammation in chicken(Gallus gallus)via modulating cytochrome P450 systems and Nrf2 mediated antioxidant defense[J]. Chemosphere, 2020, 249: 125858. doi:10.1016/j.chemosphere.2020.125858.
[32] Zarriello S, Tuazon JP, Corey S, et al. Humble beginnings with big goals: small molecule soluble epoxide hydrolase inhibitors for treating CNS disorders[J]. Prog Neurobiol, 2019, 172: 23-39. doi:10.1016/j.pneurobio.2018.11.001.
[33] Zhang J, Zhang M, Zhang WH, et al. Total flavonoids of Inula japonica alleviated the inflammatory response and oxidative stress in LPS-induced acute lung injury via inhibiting the sEH activity: insights from lipid metabolomics[J]. Phytomedicine, 2022, 107: 154380. doi:10.1016/j.phymed.2022.154380.
[34] Wagner K, Gilda J, Yang J, et al. Soluble epoxide hydrolase inhibition alleviates neuropathy in Akita(Ins2 Akita)mice[J]. Behav Brain Res, 2017, 326: 69-76. doi:10.1016/j.bbr.2017.02.048.
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