Effect of apocynin on NADPH oxidase-mediated oxidative stress-LOX-1-eNOS pathway in human endothelial cells exposed to high glucose
- PMID: 19878672
- DOI: 10.1016/j.ejphar.2009.10.045
Effect of apocynin on NADPH oxidase-mediated oxidative stress-LOX-1-eNOS pathway in human endothelial cells exposed to high glucose
Abstract
Hyperglycemia-induced generation of reactive oxygen species contributes to the development of proatherogenic changes and vasculopathy in diabetes. NADPH oxidase has been recognized as a major source of reactive oxygen species in the vasculature and the lectin-like oxLDL receptor-1 (LOX-1) appears to play a crucial role in the pathogenesis of diabetic endothelial dysfunction. The present study aimed to examine the relationships between the hyperglycemia-mediated NADPH oxidase-LOX-1 pathway activation and nitric oxide-mediated endothelial function. In addition, we investigated effect of the NADPH oxidase inhibitor, apocynin on these consequences. In human umbilical artery endothelial cells (HUAECs), the effect of high glucose on expressional regulations and functional consequences of NADPH oxidase subunits, LOX-1 and endothelial nitric oxide synthase (eNOS), in the absence and presence of apocynin (10 micromol/l) were evaluated. HUAECs were cultured under normal (5.5 mmol/l) or high glucose (30mmol/l) concentrations for 48 h in the absence and presence of apocynin. Our results showed that high glucose significantly enhanced the activity and the protein expression of NADPH oxidase subunits, Nox2 and p47(phox). High glucose markedly increased LOX-1 mRNA level and this was functionally reflected on the augmented uptake of Dil-labelled LDL (5 micromol/l, 3h) by HUAECs. Furthermore, high glucose attenuated eNOS protein and total nitrite levels. However, apocynin inhibited all these changes. Collectively, our study demonstrates that high glucose-induced oxidative stress via NADPH oxidase activation and this contributed to LOX-1 upregulation and eNOS downregulation in human endothelial cells. Apocynin efficiently reversed these consequences, suggesting its potential role as a vasculoprotective agent.
Copyright (c) 2009 Elsevier B.V. All rights reserved.
Similar articles
-
Oxidative stress and diabetic cardiovascular disorders: roles of mitochondria and NADPH oxidase.Can J Physiol Pharmacol. 2010 Mar;88(3):241-8. doi: 10.1139/Y10-018. Can J Physiol Pharmacol. 2010. PMID: 20393589 Review.
-
High glucose increases expression of cyclooxygenase-2, increases oxidative stress and decreases the generation of nitric oxide in mouse microvessel endothelial cells.J Cell Physiol. 2010 Mar;222(3):669-75. doi: 10.1002/jcp.21986. J Cell Physiol. 2010. PMID: 19950211
-
Role of LOX-1 in monocyte adhesion-triggered redox, Akt/eNOS and Ca2+ signaling pathways in endothelial cells.J Cell Physiol. 2009 Sep;220(3):706-15. doi: 10.1002/jcp.21818. J Cell Physiol. 2009. PMID: 19452449
-
Vascular NAD(P)H oxidase activation in diabetes: a double-edged sword in redox signalling.Cardiovasc Res. 2009 Apr 1;82(1):9-20. doi: 10.1093/cvr/cvp031. Epub 2009 Jan 29. Cardiovasc Res. 2009. PMID: 19179352 Review.
-
Blockade of chronic high glucose-induced endothelial apoptosis by Sasa borealis bamboo extract.Exp Biol Med (Maywood). 2008 May;233(5):580-91. doi: 10.3181/0707-RM-205. Epub 2008 Mar 28. Exp Biol Med (Maywood). 2008. PMID: 18375828
Cited by
-
The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction.Cardiovasc Diabetol. 2023 Sep 2;22(1):237. doi: 10.1186/s12933-023-01965-7. Cardiovasc Diabetol. 2023. PMID: 37660030 Free PMC article. Review.
-
Elicitation of Inhibitory Effects for AGE-Induced Oxidative Stress in Rotator Cuff-Derived Cells by Apocynin.Curr Issues Mol Biol. 2023 Apr 14;45(4):3434-3445. doi: 10.3390/cimb45040225. Curr Issues Mol Biol. 2023. PMID: 37185749 Free PMC article.
-
Native and Oxidized Low-Density Lipoproteins Increase the Expression of the LDL Receptor and the LOX-1 Receptor, Respectively, in Arterial Endothelial Cells.Cells. 2022 Jan 8;11(2):204. doi: 10.3390/cells11020204. Cells. 2022. PMID: 35053320 Free PMC article.
-
Arterial Platelet Adhesion in Atherosclerosis-Prone Arteries of Obese, Insulin-Resistant Nonhuman Primates.J Am Heart Assoc. 2021 May 4;10(9):e019413. doi: 10.1161/JAHA.120.019413. Epub 2021 Apr 21. J Am Heart Assoc. 2021. PMID: 33880941 Free PMC article.
-
Can Metformin Exert as an Active Drug on Endothelial Dysfunction in Diabetic Subjects?Biomedicines. 2020 Dec 22;9(1):3. doi: 10.3390/biomedicines9010003. Biomedicines. 2020. PMID: 33375185 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous