Login Register Cart 0
Generic placeholder image

Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Context-Dependent Regulation of Nrf2/ARE Axis on Vascular Cell Function during Hyperglycemic Condition

Author(s): Tharmarajan Ramprasath*, Allen John Freddy, Ganesan Velmurugan , Dhanendra Tomar, Balakrishnan Rekha, Vemparthan Suvekbala and Subbiah Ramasamy*

Volume 16, Issue 8, 2020

Page: [797 - 806] Pages: 10

DOI: 10.2174/1573399816666200130094512

Price: $65

conference banner
Abstract

Diabetes mellitus is associated with an increased risk of micro and macrovascular complications. During hyperglycemic conditions, endothelial cells and vascular smooth muscle cells are exquisitely sensitive to high glucose. This high glucose-induced sustained reactive oxygen species production leads to redox imbalance, which is associated with endothelial dysfunction and vascular wall remodeling. Nrf2, a redox-regulated transcription factor plays a key role in the antioxidant response element (ARE)-mediated expression of antioxidant genes. Although accumulating data indicate the molecular mechanisms underpinning the Nrf2 regulated redox balance, understanding the influence of the Nrf2/ARE axis during hyperglycemic condition on vascular cells is paramount. This review focuses on the context-dependent role of Nrf2/ARE signaling on vascular endothelial and smooth muscle cell function during hyperglycemic conditions. This review also highlights improving the Nrf2 system in vascular tissues, which could be a potential therapeutic strategy for vascular dysfunction.

Keywords: Nrf2/ARE, vascular dysfunction, smooth muscle cells, endothelial cells, phase II antioxidant enzymes, oxidative stress.

[1]
Velmurugan G, Ramprasath T, Gilles M, Swaminathan K, Ramasamy S. Gut microbiota, endocrine-disrupting chemicals, and the diabetes epidemic. Trends Endocrinol Metab 2017; 28(8): 612-25.
[http://dx.doi.org/10.1016/j.tem.2017.05.001] [PMID: 28571659]
[2]
Fox CS, Golden SH, Anderson C, et al. American Heart Association Diabetes Committee of the Council on Lifestyle and Cardiometabolic Health, Council on Clinical Cardiology, Council on Cardiovascular and Stroke Nursing, Council on Cardiovascular Surgery and Anesthesia, Council on Quality of Care and Outcomes Research, and the American Diabetes Association. Update on prevention of cardiovascular disease in adults with type 2 diabetes mellitus in light of recent evidence: A scientific statement from the American heart association and the American diabetes association. Circulation 2015; 132(8): 691-718.
[http://dx.doi.org/10.1161/CIR.0000000000000230] [PMID: 26246173]
[3]
Cade WT. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther 2008; 88(11): 1322-35.
[http://dx.doi.org/10.2522/ptj.20080008] [PMID: 18801863]
[4]
Sweileh WM. Analysis of global research output on diabetes depression and suicide. Ann Gen Psychiatry 2018; 17: 44.
[http://dx.doi.org/10.1186/s12991-018-0214-2] [PMID: 30386407]
[5]
Federation ID. IDF Diabetes Atlas. 6th ed. Brussels, Belgium: International Diabetes Federation 2013.
[6]
Mazzone T, Chait A, Plutzky J. Cardiovascular disease risk in type 2 diabetes mellitus: insights from mechanistic studies. Lancet 2008; 371(9626): 1800-9.
[http://dx.doi.org/10.1016/S0140-6736(08)60768-0] [PMID: 18502305]
[7]
Ramprasath T, Vasudevan V, Sasikumar S, Puhari SS, Saso L, Selvam GS. Regression of oxidative stress by targeting eNOS and Nrf2/ARE signaling: a guided drug target for cardiovascular diseases. Curr Top Med Chem 2015; 15(9): 857-71.
[http://dx.doi.org/10.2174/1568026615666150220114417] [PMID: 25697563]
[8]
Risbano MG, Gladwin MT. Therapeutics targeting of dysregulated redox equilibrium and endothelial dysfunction. Handb Exp Pharmacol 2013; 218: 315-49.
[http://dx.doi.org/10.1007/978-3-662-45805-1_13] [PMID: 24092346]
[9]
Li H, Horke S, Förstermann U. Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis 2014; 237(1): 208-19.
[http://dx.doi.org/10.1016/j.atherosclerosis.2014.09.001] [PMID: 25244505]
[10]
Ye ZW, Zhang J, Townsend DM, Tew KD. Oxidative stress, redox regulation and diseases of cellular differentiation. Biochim Biophys Acta 2015; 1850(8): 1607-21.
[http://dx.doi.org/10.1016/j.bbagen.2014.11.010] [PMID: 25445706]
[11]
Mandal D, Fu P, Levine AD. REDOX regulation of IL-13 signaling in intestinal epithelial cells: Usage of alternate pathways mediates distinct gene expression patterns. Cell Signal 2010; 22(10): 1485-94.
[http://dx.doi.org/10.1016/j.cellsig.2010.05.017] [PMID: 20570727]
[12]
Capellini VK, Celotto AC, Baldo CF, et al. Diabetes and vascular disease: basic concepts of nitric oxide physiology, endothelial dysfunction, oxidative stress and therapeutic possibilities. Curr Vasc Pharmacol 2010; 8(4): 526-44.
[http://dx.doi.org/10.2174/157016110791330834] [PMID: 19485895]
[13]
Ramprasath T, Murugan PS, Kalaiarasan E, Gomathi P, Rathinavel A, Selvam GS. Genetic association of Glutathione peroxidase-1 (GPx-1) and NAD(P)H:Quinone Oxidoreductase 1(NQO1) variants and their association of CAD in patients with type-2 diabetes. Mol Cell Biochem 2012; 361(1-2): 143-50.
[http://dx.doi.org/10.1007/s11010-011-1098-5] [PMID: 21989715]
[14]
Ramprasath T, Selvam GS. Potential impact of genetic variants in Nrf2 regulated antioxidant genes and risk prediction of diabetes and associated cardiac complications. Curr Med Chem 2013; 20(37): 4680-93.
[http://dx.doi.org/10.2174/09298673113209990154] [PMID: 23834171]
[15]
Ramprasath T, Senthamizharasi M, Vasudevan V, Sasikumar S, Yuvaraj S, Selvam GS. Naringenin confers protection against oxidative stress through upregulation of Nrf2 target genes in cardiomyoblast cells. J Physiol Biochem 2014; 70(2): 407-15.
[http://dx.doi.org/10.1007/s13105-014-0318-3] [PMID: 24526395]
[16]
Cullinan SB, Gordan JD, Jin J, Harper JW, Diehl JA. The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: oxidative stress sensing by a Cul3-Keap1 ligase. Mol Cell Biol 2004; 24(19): 8477-86.
[http://dx.doi.org/10.1128/MCB.24.19.8477-8486.2004] [PMID: 15367669]
[17]
Buckley BJ, Marshall ZM, Whorton AR. Nitric oxide stimulates Nrf2 nuclear translocation in vascular endothelium. Biochem Biophys Res Commun 2003; 307(4): 973-9.
[http://dx.doi.org/10.1016/S0006-291X(03)01308-1] [PMID: 12878207]
[18]
Ramprasath T, Senthil Murugan P, Prabakaran AD, Gomathi P, Rathinavel A, Selvam GS. Potential risk modifications of GSTT1, GSTM1 and GSTP1 (glutathione-S-transferases) variants and their association to CAD in patients with type-2 diabetes. Biochem Biophys Res Commun 2011; 407(1): 49-53.
[http://dx.doi.org/10.1016/j.bbrc.2011.02.097] [PMID: 21352813]
[19]
Guo J, Li C, Yang C, et al. Liraglutide reduces hepatic glucolipotoxicity induced liver cell apoptosis through NRF2 signaling in Zucker diabetic fatty rats. Mol Med Rep 2018; 17(6): 8316-24.
[http://dx.doi.org/10.3892/mmr.2018.8919] [PMID: 29693190]
[20]
Chung HT, Pae HO, Choi BM, Billiar TR, Kim YM. Nitric oxide as a bioregulator of apoptosis. Biochem Biophys Res Commun 2001; 282(5): 1075-9.
[http://dx.doi.org/10.1006/bbrc.2001.4670] [PMID: 11302723]
[21]
Ramprasath T, Kumar PH, Puhari SS, Murugan PS, Vasudevan V, Selvam GS. L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats. Biochem Biophys Res Commun 2012; 428(3): 389-94.
[http://dx.doi.org/10.1016/j.bbrc.2012.10.064] [PMID: 23103544]
[22]
Ungvari Z, Bailey-Downs L, Gautam T, et al. Adaptive induction of NF-E2-related factor-2-driven antioxidant genes in endothelial cells in response to hyperglycemia. Am J Physiol Heart Circ Physiol 2011; 300(4): H1133-40.
[http://dx.doi.org/10.1152/ajpheart.00402.2010] [PMID: 21217061]
[23]
Donovan EL, McCord JM, Reuland DJ, Miller BF, Hamilton KL. Phytochemical activation of Nrf2 protects human coronary artery endothelial cells against an oxidative challenge. Oxid Med Cell Longev 2012; 2012132931
[http://dx.doi.org/10.1155/2012/132931] [PMID: 22685617]
[24]
Ungvari Z, Bagi Z, Feher A, et al. Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2. Am J Physiol Heart Circ Physiol 2010; 299(1): H18-24.
[http://dx.doi.org/10.1152/ajpheart.00260.2010] [PMID: 20418481]
[25]
He M, Siow RC, Sugden D, Gao L, Cheng X, Mann GE. Induction of HO-1 and redox signaling in endothelial cells by advanced glycation end products: A role for Nrf2 in vascular protection in diabetes. Nutr Metab Cardiovasc Dis 2011; 21(4): 277-85.
[PMID: 20227863]
[26]
Dai G, Vaughn S, Zhang Y, Wang ET, Garcia-Cardena G, Gimbrone MA Jr. Biomechanical forces in atherosclerosis-resistant vascular regions regulate endothelial redox balance via phosphoinositol 3-kinase/Akt-dependent activation of Nrf2. Circ Res 2007; 101(7): 723-33.
[http://dx.doi.org/10.1161/CIRCRESAHA.107.152942] [PMID: 17673673]
[27]
Nyengaard JR, Ido Y, Kilo C, Williamson JR. Interactions between hyperglycemia and hypoxia: implications for diabetic retinopathy. Diabetes 2004; 53(11): 2931-8.
[http://dx.doi.org/10.2337/diabetes.53.11.2931] [PMID: 15504974]
[28]
Chapple SJ, Keeley TP, Mastronicola D, et al. Bach1 differentially regulates distinct Nrf2-dependent genes in human venous and coronary artery endothelial cells adapted to physiological oxygen levels. Free Radic Biol Med 2016; 92: 152-62.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.12.013] [PMID: 26698668]
[29]
Guo C, Xia Y, Niu P, et al. Silica nanoparticles induce oxidative stress, inflammation, and endothelial dysfunction in vitro via activation of the MAPK/Nrf2 pathway and nuclear factor-κB signaling. Int J Nanomedicine 2015; 10: 1463-77.
[http://dx.doi.org/10.2147/IJN.S76114] [PMID: 25759575]
[30]
Gomez D, Owens GK. Smooth muscle cell phenotypic switching in atherosclerosis. Cardiovasc Res 2012; 95(2): 156-64.
[http://dx.doi.org/10.1093/cvr/cvs115] [PMID: 22406749]
[31]
Grainger DJ. Transforming growth factor beta and atherosclerosis: so far, so good for the protective cytokine hypothesis. Arterioscler Thromb Vasc Biol 2004; 24(3): 399-404.
[http://dx.doi.org/10.1161/01.ATV.0000114567.76772.33] [PMID: 14699019]
[32]
Churchman AT, Anwar AA, Li FY, et al. Transforming growth factor-beta1 elicits Nrf2-mediated antioxidant responses in aortic smooth muscle cells. J Cell Mol Med 2009; 13(8B): 2282-92.
[http://dx.doi.org/10.1111/j.1582-4934.2009.00874.x] [PMID: 19674192]
[33]
Ashino T, Yamamoto M, Yoshida T, Numazawa S. Redox-sensitive transcription factor Nrf2 regulates vascular smooth muscle cell migration and neointimal hyperplasia. Arterioscler Thromb Vasc Biol 2013; 33(4): 760-8.
[http://dx.doi.org/10.1161/ATVBAHA.112.300614] [PMID: 23413426]
[34]
Roberts BR, Lim NK, McAllum EJ, et al. Oral treatment with Cu(II)(atsm) increases mutant SOD1 in vivo but protects motor neurons and improves the phenotype of a transgenic mouse model of amyotrophic lateral sclerosis. J Neurosci 2014; 34(23): 8021-31.
[http://dx.doi.org/10.1523/JNEUROSCI.4196-13.2014] [PMID: 24899723]
[35]
Srivastava S, Blower PJ, Aubdool AA, Hider RC, Mann GE, Siow RC. Cardioprotective effects of Cu(II)ATSM in human vascular smooth muscle cells and cardiomyocytes mediated by Nrf2 and DJ-1. Sci Rep 2016; 6(1): 7.
[http://dx.doi.org/10.1038/s41598-016-0012-5] [PMID: 28442712]
[36]
Otani-Takei N, Masuda T, Akimoto T, et al. Association between serum soluble klotho levels and mortality in chronic hemodialysis patients. Int J Endocrinol 2015; 2015 406269
[http://dx.doi.org/10.1155/2015/406269] [PMID: 26604925]
[37]
Maltese G, Psefteli PM, Rizzo B, et al. The anti-ageing hormone klotho induces Nrf2-mediated antioxidant defences in human aortic smooth muscle cells. J Cell Mol Med 2017; 21(3): 621-7.
[http://dx.doi.org/10.1111/jcmm.12996] [PMID: 27696667]
[38]
Freigang S, Ampenberger F, Spohn G, et al. Nrf2 is essential for cholesterol crystal-induced inflammasome activation and exacerbation of atherosclerosis. Eur J Immunol 2011; 41(7): 2040-51.
[http://dx.doi.org/10.1002/eji.201041316] [PMID: 21484785]
[39]
Tan Y, Ichikawa T, Li J, et al. Diabetic downregulation of Nrf2 activity via ERK contributes to oxidative stress-induced insulin resistance in cardiac cells in vitro and in vivo. Diabetes 2011; 60(2): 625-33.
[http://dx.doi.org/10.2337/db10-1164] [PMID: 21270272]
[40]
Eurich DT, Majumdar SR, Tsuyuki RT, Johnson JA. Reduced mortality associated with the use of ACE inhibitors in patients with type 2 diabetes. Diabetes Care 2004; 27(6): 1330-4.
[http://dx.doi.org/10.2337/diacare.27.6.1330] [PMID: 15161784]
[41]
Lindholm LH, Ibsen H, Borch-Johnsen K, et al. LIFE study group. Risk of new-onset diabetes in the Losartan Intervention For Endpoint reduction in hypertension study. J Hypertens 2002; 20(9): 1879-86.
[http://dx.doi.org/10.1097/00004872-200209000-00035] [PMID: 12195132]
[42]
Turan B, Vassort G. Ryanodine receptor: a new therapeutic target to control diabetic cardiomyopathy. Antioxid Redox Signal 2011; 15(7): 1847-61.
[http://dx.doi.org/10.1089/ars.2010.3725] [PMID: 21091075]
[43]
Chen J, Zhang Z, Cai L. Diabetic cardiomyopathy and its prevention by nrf2: current status. Diabetes Metab J 2014; 38(5): 337-45.
[http://dx.doi.org/10.4093/dmj.2014.38.5.337] [PMID: 25349820]
[44]
Zhu A, Wei X, Zhang Y, et al. Propofol provides cardiac protection by suppressing the proteasome degradation of caveolin-3 in ischemic/reperfused rat hearts. J Cardiovasc Pharmacol 2017; 69(3): 170-7.
[http://dx.doi.org/10.1097/FJC.0000000000000454] [PMID: 28009721]
[45]
Shinjo T, Tanaka T, Okuda H, et al. Propofol induces nuclear localization of Nrf2 under conditions of oxidative stress in cardiac H9c2 cells. PLoS One 2018; 13(4) e0196191
[http://dx.doi.org/10.1371/journal.pone.0196191] [PMID: 29689082]
[46]
Xu B, Zhang J, Strom J, Lee S, Chen QM. Myocardial ischemic reperfusion induces de novo Nrf2 protein translation. Biochim Biophys Acta 2014; 1842(9): 1638-47.
[http://dx.doi.org/10.1016/j.bbadis.2014.06.002] [PMID: 24915518]
[47]
Yan WJ, Dong HL, Xiong LZ. The protective roles of autophagy in ischemic preconditioning. Acta Pharmacol Sin 2013; 34(5): 636-43.
[http://dx.doi.org/10.1038/aps.2013.18] [PMID: 23603984]
[48]
Agca CA, Tuzcu M, Hayirli A, Sahin K. Taurine ameliorates neuropathy via regulating NF-κB and Nrf2/HO-1 signaling cascades in diabetic rats. Food Chem Toxicol 2014; 71: 116-21.
[http://dx.doi.org/10.1016/j.fct.2014.05.023] [PMID: 24907624]
[49]
Yama K, Sato K, Abe N, Murao Y, Tatsunami R, Tampo Y. Epalrestat increases glutathione, thioredoxin, and heme oxygenase-1 by stimulating Nrf2 pathway in endothelial cells. Redox Biol 2015; 4: 87-96.
[http://dx.doi.org/10.1016/j.redox.2014.12.002] [PMID: 25529839]
[50]
Negi G, Kumar A, Sharma SS. Melatonin modulates neuroinflammation and oxidative stress in experimental diabetic neuropathy: effects on NF-κB and Nrf2 cascades. J Pineal Res 2011; 50(2): 124-31.
[PMID: 21062351]
[51]
Furukawa M, Xiong Y. BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase. Mol Cell Biol 2005; 25(1): 162-71.
[http://dx.doi.org/10.1128/MCB.25.1.162-171.2005] [PMID: 15601839]
[52]
Brownlee M. The pathobiology of diabetic complications: A unifying mechanism. Diabetes 2005; 54(6): 1615-25.
[http://dx.doi.org/10.2337/diabetes.54.6.1615] [PMID: 15919781]
[53]
Zhong Q, Mishra M, Kowluru RA. Transcription factor Nrf2-mediated antioxidant defense system in the development of diabetic retinopathy. Invest Ophthalmol Vis Sci 2013; 54(6): 3941-8.
[http://dx.doi.org/10.1167/iovs.13-11598] [PMID: 23633659]
[54]
Xu Z, Wei Y, Gong J, et al. NRF2 plays a protective role in diabetic retinopathy in mice. Diabetologia 2014; 57(1): 204-13.
[http://dx.doi.org/10.1007/s00125-013-3093-8] [PMID: 24186494]
[55]
Wei Y, Gong J, Yoshida T, et al. Nrf2 has a protective role against neuronal and capillary degeneration in retinal ischemia-reperfusion injury. Free Radic Biol Med 2011; 51(1): 216-24.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.04.026] [PMID: 21545836]
[56]
Zheng H, Whitman SA, Wu W, et al. Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy. Diabetes 2011; 60(11): 3055-66.
[http://dx.doi.org/10.2337/db11-0807] [PMID: 22025779]
[57]
Jiang T, Huang Z, Lin Y, Zhang Z, Fang D, Zhang DD. The protective role of Nrf2 in streptozotocin-induced diabetic nephropathy. Diabetes 2010; 59(4): 850-60.
[http://dx.doi.org/10.2337/db09-1342] [PMID: 20103708]
[58]
Sakamuri SSVP, Sperling JA, Sure VN, et al. Measurement of respiratory function in isolated cardiac mitochondria using Seahorse XFe24 Analyzer: Applications for aging research. Geroscience 2018; 40(3): 347-56.
[http://dx.doi.org/10.1007/s11357-018-0021-3] [PMID: 29860557]
[59]
Sure VN, Sakamuri SSVP, Sperling JA, et al. A novel high-throughput assay for respiration in isolated brain microvessels reveals impaired mitochondrial function in the aged mice. Geroscience 2018; 40(4): 365-75.
[http://dx.doi.org/10.1007/s11357-018-0037-8] [PMID: 30074132]
[60]
Ungvari Z, Bailey-Downs L, Gautam T, et al. Age-associated vascular oxidative stress, Nrf2 dysfunction, and NF-kappaB activation in the nonhuman primate Macaca mulatta. J Gerontol A Biol Sci Med Sci 2011; 66(8): 866-75.
[http://dx.doi.org/10.1093/gerona/glr092] [PMID: 21622983]
[61]
Shih PH, Yen GC. Differential expressions of antioxidant status in aging rats: the role of transcriptional factor Nrf2 and MAPK signaling pathway. Biogerontology 2007; 8(2): 71-80.
[http://dx.doi.org/10.1007/s10522-006-9033-y] [PMID: 16850181]
[62]
Tsakiri EN, Sykiotis GP, Papassideri IS, et al. Proteasome dysfunction in Drosophila signals to an Nrf2-dependent regulatory circuit aiming to restore proteostasis and prevent premature aging. Aging Cell 2013; 12(5): 802-13.
[http://dx.doi.org/10.1111/acel.12111] [PMID: 23738891]
[63]
Rahman MM, Sykiotis GP, Nishimura M, Bodmer R, Bohmann D. Declining signal dependence of Nrf2-MafS-regulated gene expression correlates with aging phenotypes. Aging Cell 2013; 12(4): 554-62.
[http://dx.doi.org/10.1111/acel.12078] [PMID: 23521918]
[64]
Gao B, Doan A, Hybertson BM. The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders. Clin Pharmacol 2014; 6: 19-34.
[PMID: 24520207]
[65]
Suzuki T, Motohashi H, Yamamoto M. Toward clinical application of the Keap1-Nrf2 pathway. Trends Pharmacol Sci 2013; 34(6): 340-6.
[http://dx.doi.org/10.1016/j.tips.2013.04.005] [PMID: 23664668]
[66]
Schulze-Topphoff U, Varrin-Doyer M, Pekarek K, et al. Dimethyl fumarate treatment induces adaptive and innate immune modulation independent of Nrf2. Proc Natl Acad Sci USA 2016; 113(17): 4777-82.
[http://dx.doi.org/10.1073/pnas.1603907113] [PMID: 27078105]
[67]
Hammer A, Waschbisch A, Kuhbandner K, et al. The NRF2 pathway as potential biomarker for dimethyl fumarate treatment in multiple sclerosis. Ann Clin Transl Neurol 2018; 5(6): 668-76.
[http://dx.doi.org/10.1002/acn3.553] [PMID: 29928650]
[68]
Matzinger M, Fischhuber K, Heiss EH. Activation of Nrf2 signaling by natural products-can it alleviate diabetes? Biotechnol Adv 2018; 36(6): 1738-67.
[http://dx.doi.org/10.1016/j.biotechadv.2017.12.015] [PMID: 29289692]
[69]
Shahzad K, Bock F, Al-Dabet MM, et al. Stabilization of endogenous Nrf2 by minocycline protects against Nlrp3-inflammasome induced diabetic nephropathy. Sci Rep 2016; 6: 34228.
[http://dx.doi.org/10.1038/srep34228] [PMID: 27721446]

Rights & Permissions Print Cite
Article Metrics
28
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy