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Effect of apocynin on NADPH oxidase-mediated oxidative stress-LOX-1-eNOS pathway in human endothelial cells exposed to high glucose.
Eur J Pharmacol. 2010 Feb 10; 627(1-3):42-8.EJ

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.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Egypt. Ashraf_taye70@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19878672

Citation

Taye, Ashraf, et al. "Effect of Apocynin On NADPH Oxidase-mediated Oxidative stress-LOX-1-eNOS Pathway in Human Endothelial Cells Exposed to High Glucose." European Journal of Pharmacology, vol. 627, no. 1-3, 2010, pp. 42-8.
Taye A, Saad AH, Kumar AH, et al. Effect of apocynin on NADPH oxidase-mediated oxidative stress-LOX-1-eNOS pathway in human endothelial cells exposed to high glucose. Eur J Pharmacol. 2010;627(1-3):42-8.
Taye, A., Saad, A. H., Kumar, A. H., & Morawietz, H. (2010). Effect of apocynin on NADPH oxidase-mediated oxidative stress-LOX-1-eNOS pathway in human endothelial cells exposed to high glucose. European Journal of Pharmacology, 627(1-3), 42-8. https://doi.org/10.1016/j.ejphar.2009.10.045
Taye A, et al. Effect of Apocynin On NADPH Oxidase-mediated Oxidative stress-LOX-1-eNOS Pathway in Human Endothelial Cells Exposed to High Glucose. Eur J Pharmacol. 2010 Feb 10;627(1-3):42-8. PubMed PMID: 19878672.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of apocynin on NADPH oxidase-mediated oxidative stress-LOX-1-eNOS pathway in human endothelial cells exposed to high glucose. AU - Taye,Ashraf, AU - Saad,Adel H, AU - Kumar,Arun Hs, AU - Morawietz,Henning, Y1 - 2009/10/28/ PY - 2009/05/27/received PY - 2009/09/21/revised PY - 2009/10/14/accepted PY - 2009/11/3/entrez PY - 2009/11/3/pubmed PY - 2010/4/7/medline SP - 42 EP - 8 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 627 IS - 1-3 N2 - 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. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/19878672/Effect_of_apocynin_on_NADPH_oxidase_mediated_oxidative_stress_LOX_1_eNOS_pathway_in_human_endothelial_cells_exposed_to_high_glucose_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(09)00952-2 DB - PRIME DP - Unbound Medicine ER -