Pyrroloquinoline Quinone Protects Mouse Brain Endothelial Cells from High Glucose-induced Damage in Vitro

Overview

Journal Acta Pharmacol Sin

Specialty Pharmacology

Date 2014 Oct 7

PMID 25283505

Citations 5

Authors

Zhong Wang

Guo-Qiang Chen

Gui-Ping Yu

Chang-Jian Liu

Affiliations

Soon will be listed here.

Abstract

Aim: To investigate the effects of pyrroloquinoline quinone (PQQ), an oxidoreductase cofactor, on high glucose-induced mouse endothelial cell damage in vitro.

Methods: Mouse brain microvascular endothelial bEND.3 cells were exposed to different glucose concentrations (5.56, 25 and 40 mmol/L) for 24 or 48 h. The cell viability was examined using MTT assay. Flow cytometry was used to analyze the apoptosis and ROS levels in the cells. MitoTracker Green staining was used to examine the mitochondria numbers in the cells. Western blot analysis was used to analyze the expression of HIF-1α and the proteins in JNK pathway.

Results: Treatment of bEND.3 cells with high glucose significantly decreased the cell viability, while addition of PQQ (1 and 10 μmol/L) reversed the high glucose-induced cell damage in a concentration-dependent manner. Furthermore, PQQ (100 μmol/L) significantly suppressed the high glucose-induced apoptosis and ROS production in the cells. PQQ significantly reversed the high glucose-induced reduction in both the mitochondrial membrane potential and mitochondria number in the cells. The high glucose treatment significantly increased the expression of HIF-1α and JNK phosphorylation in the cells, and addition of PQQ led to a further increase of HIF-1α level and a decrease of JNK phosphorylation. Addition of JNK inhibitor SP600125 (10 μmol/L) also significantly suppressed high glucose-induced apoptosis and JNK phosphorylation in bEND.3 cells.

Conclusion: PQQ protects mouse brain endothelial cells from high glucose damage in vitro by suppressing intracellular ROS and apoptosis via inhibiting JNK signaling pathway.

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References

Nakao Y, Teramukai S, Tanaka S, Yasuno S, Fujimoto A, Kasahara M . Effects of renin-angiotensin system blockades on cardiovascular outcomes in patients with diabetes mellitus: A systematic review and meta-analysis. Diabetes Res Clin Pract. 2011; 96(1):68-75. DOI: 10.1016/j.diabres.2011.11.025. View

Garabedian T, Alam S . High residual platelet reactivity on clopidogrel: its significance and therapeutic challenges overcoming clopidogrel resistance. Cardiovasc Diagn Ther. 2013; 3(1):23-37. PMC: 3839215. DOI: 10.3978/j.issn.2223-3652.2013.02.06. View

Cubbon R, Ali N, Sengupta A, Kearney M . Insulin- and growth factor-resistance impairs vascular regeneration in diabetes mellitus. Curr Vasc Pharmacol. 2012; 10(3):271-84. DOI: 10.2174/157016112799959305. View

Onat D, Brillon D, Colombo P, Schmidt A . Human vascular endothelial cells: a model system for studying vascular inflammation in diabetes and atherosclerosis. Curr Diab Rep. 2011; 11(3):193-202. PMC: 3311155. DOI: 10.1007/s11892-011-0182-2. View

Thomas M . Advanced glycation end products. Contrib Nephrol. 2011; 170:66-74. DOI: 10.1159/000324945. View

Zhang S, Chen X, Yang Y, Zhou X, Liu J, Ding F . Neuroprotection against cobalt chloride-induced cell apoptosis of primary cultured cortical neurons by salidroside. Mol Cell Biochem. 2011; 354(1-2):161-70. DOI: 10.1007/s11010-011-0815-4. View

Potenza M, Gagliardi S, Nacci C, Carratu M, Montagnani M . Endothelial dysfunction in diabetes: from mechanisms to therapeutic targets. Curr Med Chem. 2009; 16(1):94-112. DOI: 10.2174/092986709787002853. View

Tousoulis D, Kampoli A, Tentolouris C, Papageorgiou N, Stefanadis C . The role of nitric oxide on endothelial function. Curr Vasc Pharmacol. 2011; 10(1):4-18. DOI: 10.2174/157016112798829760. View

Pandey A, Tripathi P, Pandey R, Srivatava R, Goswami S . Alternative therapies useful in the management of diabetes: A systematic review. J Pharm Bioallied Sci. 2012; 3(4):504-12. PMC: 3249697. DOI: 10.4103/0975-7406.90103. View

10.

Yan J, Zhang Z, Shi H . HIF-1 is involved in high glucose-induced paracellular permeability of brain endothelial cells. Cell Mol Life Sci. 2011; 69(1):115-28. PMC: 11115066. DOI: 10.1007/s00018-011-0731-5. View

11.

Gomez-Manzo S, Contreras-Zentella M, Gonzalez-Valdez A, Sosa-Torres M, Arreguin-Espinoza R, Escamilla-Marvan E . The PQQ-alcohol dehydrogenase of Gluconacetobacter diazotrophicus. Int J Food Microbiol. 2008; 125(1):71-8. DOI: 10.1016/j.ijfoodmicro.2007.10.015. View

12.

Zhang L, Pang S, Deng B, Qian L, Chen J, Zou J . High glucose induces renal mesangial cell proliferation and fibronectin expression through JNK/NF-κB/NADPH oxidase/ROS pathway, which is inhibited by resveratrol. Int J Biochem Cell Biol. 2012; 44(4):629-38. DOI: 10.1016/j.biocel.2012.01.001. View

13.

Szabo C . Roles of hydrogen sulfide in the pathogenesis of diabetes mellitus and its complications. Antioxid Redox Signal. 2011; 17(1):68-80. PMC: 4701125. DOI: 10.1089/ars.2011.4451. View

14.

Misra H, Khairnar N, Barik A, Priyadarsini K, Mohan H, Apte S . Pyrroloquinoline-quinone: a reactive oxygen species scavenger in bacteria. FEBS Lett. 2004; 578(1-2):26-30. DOI: 10.1016/j.febslet.2004.10.061. View

15.

Ho S, Wu W, Chiu H, Chen Y, Ho Y, Guo H . Arsenic trioxide and radiation enhance apoptotic effects in HL-60 cells through increased ROS generation and regulation of JNK and p38 MAPK signaling pathways. Chem Biol Interact. 2011; 193(2):162-71. DOI: 10.1016/j.cbi.2011.06.007. View

16.

Toda N, Nakanishi-Toda M . Nitric oxide: ocular blood flow, glaucoma, and diabetic retinopathy. Prog Retin Eye Res. 2007; 26(3):205-38. DOI: 10.1016/j.preteyeres.2007.01.004. View

17.

Tousoulis D, Briasoulis A, Papageorgiou N, Tsioufis C, Tsiamis E, Toutouzas K . Oxidative stress and endothelial function: therapeutic interventions. Recent Pat Cardiovasc Drug Discov. 2011; 6(2):103-14. DOI: 10.2174/157489011795933819. View

18.

Kishida K, Funahashi T, Shimomura I . Molecular mechanisms of diabetes and atherosclerosis: role of adiponectin. Endocr Metab Immune Disord Drug Targets. 2012; 12(2):118-31. DOI: 10.2174/187153012800493468. View

19.

Yoon J, Cho B, Park H, Kang S, Choi S, Jang H . Differential effects of trimetazidine on vascular smooth muscle cell and endothelial cell in response to carotid artery balloon injury in diabetic rats. Int J Cardiol. 2012; 167(1):126-33. DOI: 10.1016/j.ijcard.2011.12.061. View

20.

Holscher T, Schleyer U, Merfort M, Bringer-Meyer S, Gorisch H, Sahm H . Glucose oxidation and PQQ-dependent dehydrogenases in Gluconobacter oxydans. J Mol Microbiol Biotechnol. 2008; 16(1-2):6-13. DOI: 10.1159/000142890. View