Quercetin protects against high glucose-induced damage in bone marrow-derived endothelial progenitor cells

Zhao,Li-Rong; Du,Yu-Jun; Chen,Lei; Liu,Zhi-Gang; Pan,Yue-Hai; Liu,Jian-Feng; Liu,Bin

doi:10.3892/ijmm.2014.1852

Quercetin protects against high glucose-induced damage in bone marrow-derived endothelial progenitor cells

Authors:
- Li-Rong Zhao
- Yu-Jun Du
- Lei Chen
- Zhi-Gang Liu
- Yue-Hai Pan
- Jian-Feng Liu
- Bin Liu
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Affiliations: Department of Ultrasound, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Nephrology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Hand Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: July 14, 2014 https://doi.org/10.3892/ijmm.2014.1852
Pages: 1025-1031

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Abstract

Endothelial progenitor cells (EPCs), a group of bone marrow-derived pro-angiogenic cells, contribute to vascular repair after damage. EPC dysfunction exists in diabetes and results in poor wound healing in diabetic patients with trauma or surgery. The aim of the present study was to determine the effect of quercetin, a natural flavonoid on high glucose‑induced damage in EPCs. Treatment with high glucose (40 mM) decreased cell viability and migration, and increased oxidant stress, as was evidenced by the elevated levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase in bone marrow-derived EPCs. Moreover, high glucose reduced the levels of endothelial nitric oxide synthase (eNOS) phosphorylation, nitric oxide (NO) production and intracellular cyclic guanosine monophosphate (cGMP). Quercetin supplement protected against high glucose‑induced impairment in cell viability, migration, oxidant stress, eNOS phosphorylation, NO production and cGMP levels. Quercetin also increased Sirt1 expression in EPCs. Inhibition of Sirt1 by a chemical antagonist sirtinol abolished the protective effect of quercetin on eNOS phosphorylation, NO production and cGMP levels following high glucose stress. To the best of our knowledge, the results provide the first evidence that quercetin protects against high glucose‑induced damage by inducing Sirt1-dependent eNOS upregulation in EPCs, and suggest that quercetin is a promising therapeutic agent for diabetic patients undergoing surgery or other invasive procedures.

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1	Asahara T, Murohara T, Sullivan A, et al: Isolation of putative progenitor endothelial cells for angiogenesis. Science. 275:964–967. 1997. View Article : Google Scholar : PubMed/NCBI
2	Hristov M, Erl W and Weber PC: Endothelial progenitor cells: mobilization, differentiation, and homing. Arterioscler Thromb Vasc Biol. 23:1185–1189. 2003. View Article : Google Scholar : PubMed/NCBI
3	Hristov M and Weber C: Endothelial progenitor cells: characterization, pathophysiology, and possible clinical relevance. J Cell Mol Med. 8:498–508. 2004. View Article : Google Scholar : PubMed/NCBI
4	Loomans CJ, de Koning EJ, Staal FJ, et al: Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes. 53:195–199. 2004. View Article : Google Scholar : PubMed/NCBI
5	Fadini GP, Miorin M, Facco M, et al: Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol. 45:1449–1457. 2005. View Article : Google Scholar : PubMed/NCBI
6	Sorrentino SA, Bahlmann FH, Besler C, et al: Oxidant stress impairs in vivo reendothelialization capacity of endothelial progenitor cells from patients with type 2 diabetes mellitus: restoration by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. Circulation. 116:163–173. 2007. View Article : Google Scholar
7	Rosso A, Balsamo A, Gambino R, et al: p53 Mediates the accelerated onset of senescence of endothelial progenitor cells in diabetes. J Biol Chem. 281:4339–4347. 2006. View Article : Google Scholar : PubMed/NCBI
8	Hamed S, Brenner B and Roguin A: Nitric oxide: a key factor behind the dysfunctionality of endothelial progenitor cells in diabetes mellitus type-2. Cardiovasc Res. 91:9–15. 2011. View Article : Google Scholar : PubMed/NCBI
9	van Dam RM, Naidoo N and Landberg R: Dietary flavonoids and the development of type 2 diabetes and cardiovascular diseases: review of recent findings. Curr Opin Lipidol. 24:25–33. 2013.PubMed/NCBI
10	Nicolle E, Souard F, Faure P and Boumendjel A: Flavonoids as promising lead compounds in type 2 diabetes mellitus: molecules of interest and structure-activity relationship. Curr Med Chem. 18:2661–2672. 2011. View Article : Google Scholar : PubMed/NCBI
11	Formica JV and Regelson W: Review of the biology of Quercetin and related bioflavonoids. Food Chem Toxicol. 33:1061–1080. 1995. View Article : Google Scholar : PubMed/NCBI
12	Kim JH, Kang MJ, Choi HN, Jeong SM, Lee YM and Kim JI: Quercetin attenuates fasting and postprandial hyperglycemia in animal models of diabetes mellitus. Nutr Res Pract. 5:107–111. 2011. View Article : Google Scholar : PubMed/NCBI
13	Margina D, Gradinaru D, Manda G, Neagoe I and Ilie M: Membranar effects exerted in vitro by polyphenols - quercetin, epigallocatechin gallate and curcumin - on HUVEC and Jurkat cells, relevant for diabetes mellitus. Food Chem Toxicol. 61:86–93. 2013. View Article : Google Scholar
14	Mahmoud MF, Hassan NA, El Bassossy HM and Fahmy A: Quercetin protects against diabetes-induced exaggerated vasoconstriction in rats: effect on low grade inflammation. PloS One. 8:e637842013. View Article : Google Scholar : PubMed/NCBI
15	Zahedi M, Ghiasvand R, Feizi A, Asgari G and Darvish L: Does quercetin improve cardiovascular risk factors and inflammatory biomarkers in women with type 2 diabetes: a double-blind randomized controlled clinical trial. Int J Prev Med. 4:777–785. 2013.PubMed/NCBI
16	Marrotte EJ, Chen DD, Hakim JS and Chen AF: Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice. J Clin Invest. 120:4207–4219. 2010. View Article : Google Scholar : PubMed/NCBI
17	Wang P, Xu TY, Guan YF, Su DF, Fan GR and Miao CY: Perivascular adipose tissue-derived visfatin is a vascular smooth muscle cell growth factor: role of nicotinamide mononucleotide. Cardiovasc Res. 81:370–380. 2009. View Article : Google Scholar : PubMed/NCBI
18	Wang P, Guan YF, Du H, Zhai QW, Su DF and Miao CY: Induction of autophagy contributes to the neuroprotection of nicotinamide phosphoribosyltransferase in cerebral ischemia. Autophagy. 8:77–87. 2012. View Article : Google Scholar : PubMed/NCBI
19	Liu BQ, Du ZX, Zong ZH, et al: BAG3-dependent noncanonical autophagy induced by proteasome inhibition in HepG2 cells. Autophagy. 9:905–916. 2013. View Article : Google Scholar : PubMed/NCBI
20	Garg AD, Dudek AM, Ferreira GB, et al: ROS-induced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death. Autophagy. 9:1292–1307. 2013. View Article : Google Scholar : PubMed/NCBI
21	Zhang XH, Lei H, Liu AJ, Zou YX, Shen FM and Su DF: Increased oxidative stress is responsible for severer cerebral infarction in stroke-prone spontaneously hypertensive rats. CNS Neurosci Ther. 17:590–598. 2011. View Article : Google Scholar : PubMed/NCBI
22	Schmeisser H, Fey SB, Horowitz J, et al: Type I interferons induce autophagy in certain human cancer cell lines. Autophagy. 9:683–696. 2013. View Article : Google Scholar : PubMed/NCBI
23	Luciani A, Villella VR, Esposito S, et al: Targeting autophagy as a novel strategy for facilitating the therapeutic action of potentiators on DeltaF508 cystic fibrosis transmembrane conductance regulator. Autophagy. 8:1657–1672. 2012. View Article : Google Scholar
24	Wang P, Zhang RY, Song J, et al: Loss of AMP-activated protein kinase-alpha2 impairs the insulin-sensitizing effect of calorie restriction in skeletal muscle. Diabetes. 61:1051–1061. 2012. View Article : Google Scholar : PubMed/NCBI
25	Wang P, Xu TY, Guan YF, et al: Nicotinamide phosphoribosyltransferase protects against ischemic stroke through SIRT1-dependent adenosine monophosphate-activated kinase pathway. Ann Neurol. 69:360–374. 2011. View Article : Google Scholar
26	Oh JM, Choi EK, Carp RI and Kim YS: Oxidative stress impairs autophagic flux in prion protein-deficient hippocampal cells. Autophagy. 8:1448–1461. 2012. View Article : Google Scholar : PubMed/NCBI
27	Zhang T, Li Y, Park KA, et al: Cucurbitacin induces autophagy through mitochondrial ROS production which counteracts to limit caspase-dependent apoptosis. Autophagy. 8:559–576. 2012. View Article : Google Scholar
28	Song YM, Song SO, Jung YK, et al: Dimethyl sulfoxide reduces hepatocellular lipid accumulation through autophagy induction. Autophagy. 8:1085–1097. 2012. View Article : Google Scholar : PubMed/NCBI
29	Zhao YD, Courtman DW, Deng Y, Kugathasan L, Zhang Q and Stewart DJ: Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: efficacy of combined cell and eNOS gene therapy in established disease. Circ Res. 96:442–450. 2005. View Article : Google Scholar
30	Duda DG, Fukumura D and Jain RK: Role of eNOS in neovascularization: NO for endothelial progenitor cells. Trends Mol Med. 10:143–145. 2004. View Article : Google Scholar : PubMed/NCBI
31	Mattagajasingh I, Kim CS, Naqvi A, et al: SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc Natl Acad Sci USA. 104:14855–14860. 2007. View Article : Google Scholar
32	Chao CL, Hou YC, Chao PD, Weng CS and Ho FM: The antioxidant effects of quercetin metabolites on the prevention of high glucose-induced apoptosis of human umbilical vein endothelial cells. Br J Nutr. 101:1165–1170. 2009. View Article : Google Scholar : PubMed/NCBI
33	Bournival J, Francoeur MA, Renaud J and Martinoli MG: Quercetin and sesamin protect neuronal PC12 cells from high-glucose-induced oxidation, nitrosative stress, and apoptosis. Rejuvenation Res. 15:322–333. 2012. View Article : Google Scholar : PubMed/NCBI
34	Shi Y, Liang XC, Zhang H, Wu QL, Qu L and Sun Q: Quercetin protects rat dorsal root ganglion neurons against high glucose-induced injury in vitro through Nrf-2/HO-1 activation and NF-kappaB inhibition. Acta Pharmacol Sin. 34:1140–1148. 2013. View Article : Google Scholar : PubMed/NCBI
35	Chen YH, Lin SJ, Lin FY, et al: High glucose impairs early and late endothelial progenitor cells by modifying nitric oxide-related but not oxidative stress-mediated mechanisms. Diabetes. 56:1559–1568. 2007. View Article : Google Scholar : PubMed/NCBI
36	Kobayashi S, Xu X, Chen K and Liang Q: Suppression of autophagy is protective in high glucose-induced cardiomyocyte injury. Autophagy. 8:577–592. 2012. View Article : Google Scholar : PubMed/NCBI
37	Thum T, Fraccarollo D, Schultheiss M, et al: Endothelial nitric oxide synthase uncoupling impairs endothelial progenitor cell mobilization and function in diabetes. Diabetes. 56:666–674. 2007. View Article : Google Scholar : PubMed/NCBI
38	Herranz D and Serrano M: SIRT1: recent lessons from mouse models. Nat Rev Cancer. 10:819–823. 2010. View Article : Google Scholar : PubMed/NCBI
39	Balestrieri ML, Rienzo M, Felice F, et al: High glucose downregulates endothelial progenitor cell number via SIRT1. Biochim Biophys Acta. 1784:936–945. 2008. View Article : Google Scholar : PubMed/NCBI
40	Servillo L, D’Onofrio N, Longobardi L, et al: Stachydrine ameliorates high-glucose induced endothelial cell senescence and SIRT1 downregulation. J Cell Biochem. 114:2522–2530. 2013. View Article : Google Scholar : PubMed/NCBI
41	Davis JM, Murphy EA, Carmichael MD and Davis B: Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol. 296:R1071–R1077. 2009. View Article : Google Scholar : PubMed/NCBI
42	Casuso RA, Martinez-Lopez EJ, Nordsborg NB, et al: Oral quercetin supplementation hampers skeletal muscle adaptations in response to exercise training. Scand J Med Sci Sports. Oct 14–2013.(E-pub ahead of print).