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Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells.
Redox Biol 2014; 2:570-9RB

Abstract

NADPH oxidases are the major sources of reactive oxygen species in cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents. Because Nox isoforms in renal proximal tubules (RPTs) are involved in the pathogenesis of hypertension, we tested the hypothesis that NOX5 is differentially expressed in RPT cells from normotensive (NT) and hypertensive subjects (HT). We found that NOX5 mRNA, total NOX5 protein, and apical membrane NOX5 protein were 4.2±0.7-fold, 5.2±0.7-fold, and 2.8±0.5-fold greater in HT than NT. Basal total NADPH oxidase activity was 4.5±0.2-fold and basal NOX5 activity in NOX5 immunoprecipitates was 6.2±0.2-fold greater in HT than NT (P=<0.001, n=6-14/group). Ionomycin increased total NOX and NOX5 activities in RPT cells from HT (P<0.01, n=4, ANOVA), effects that were abrogated by pre-treatment of the RPT cells with diphenylene-iodonium or superoxide dismutase. Silencing NOX5 using NOX5-siRNA decreased NADPH oxidase activity (-45.1±3.2% vs. mock-siRNA, n=6-8) in HT. D1-like receptor stimulation decreased NADPH oxidase activity to a greater extent in NT (-32.5±1.8%) than HT (-14.8±1.8). In contrast to the marked increase in expression and activity of NOX5 in HT, NOX1 mRNA and protein were minimally increased in HT, relative to NT; total NOX2 and NOX4 proteins were not different between HT and NT, while the increase in apical RPT cell membrane NOX1, NOX2, and NOX4 proteins in HT, relative to NT, was much less than those observed with NOX5. Thus, we demonstrate, for the first time, that NOX5 is expressed in human RPT cells and to greater extent than the other Nox isoforms in HT than NT. We suggest that the increased expression of NOX5, which may be responsible for the increased oxidative stress in RPT cells in human essential hypertension, is caused, in part, by a defective renal dopaminergic system.

Authors+Show Affiliations

Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.Department of Cardiovascular Medicine, The First Hospital Affiliated to Anhui Medical University, Hefei, Anhui, PR China.Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.Department of Pediatrics, Georgetown University Medical Center, Washington, DC, USA.Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.Department of Immunology and Infectious Diseases, Montana State University, Bozeman, MT, USA.Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, VA, USA.Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, VA, USA.Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA ; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24688893

Citation

Yu, Peiying, et al. "Unique Role of NADPH Oxidase 5 in Oxidative Stress in Human Renal Proximal Tubule Cells." Redox Biology, vol. 2, 2014, pp. 570-9.
Yu P, Han W, Villar VA, et al. Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells. Redox Biol. 2014;2:570-9.
Yu, P., Han, W., Villar, V. A., Yang, Y., Lu, Q., Lee, H., ... Jose, P. A. (2014). Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells. Redox Biology, 2, pp. 570-9. doi:10.1016/j.redox.2014.01.020.
Yu P, et al. Unique Role of NADPH Oxidase 5 in Oxidative Stress in Human Renal Proximal Tubule Cells. Redox Biol. 2014;2:570-9. PubMed PMID: 24688893.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells. AU - Yu,Peiying, AU - Han,Weixing, AU - Villar,Van Anthony M, AU - Yang,Yu, AU - Lu,Quansheng, AU - Lee,Hewang, AU - Li,Fengmin, AU - Quinn,Mark T, AU - Gildea,John J, AU - Felder,Robin A, AU - Jose,Pedro A, Y1 - 2014/02/22/ PY - 2013/12/26/received PY - 2014/01/28/revised PY - 2014/01/30/accepted PY - 2014/4/2/entrez PY - 2014/4/2/pubmed PY - 2014/4/2/medline KW - Dopamine receptor KW - NOX5 KW - Oxidative stress KW - ROS SP - 570 EP - 9 JF - Redox biology JO - Redox Biol VL - 2 N2 - NADPH oxidases are the major sources of reactive oxygen species in cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents. Because Nox isoforms in renal proximal tubules (RPTs) are involved in the pathogenesis of hypertension, we tested the hypothesis that NOX5 is differentially expressed in RPT cells from normotensive (NT) and hypertensive subjects (HT). We found that NOX5 mRNA, total NOX5 protein, and apical membrane NOX5 protein were 4.2±0.7-fold, 5.2±0.7-fold, and 2.8±0.5-fold greater in HT than NT. Basal total NADPH oxidase activity was 4.5±0.2-fold and basal NOX5 activity in NOX5 immunoprecipitates was 6.2±0.2-fold greater in HT than NT (P=<0.001, n=6-14/group). Ionomycin increased total NOX and NOX5 activities in RPT cells from HT (P<0.01, n=4, ANOVA), effects that were abrogated by pre-treatment of the RPT cells with diphenylene-iodonium or superoxide dismutase. Silencing NOX5 using NOX5-siRNA decreased NADPH oxidase activity (-45.1±3.2% vs. mock-siRNA, n=6-8) in HT. D1-like receptor stimulation decreased NADPH oxidase activity to a greater extent in NT (-32.5±1.8%) than HT (-14.8±1.8). In contrast to the marked increase in expression and activity of NOX5 in HT, NOX1 mRNA and protein were minimally increased in HT, relative to NT; total NOX2 and NOX4 proteins were not different between HT and NT, while the increase in apical RPT cell membrane NOX1, NOX2, and NOX4 proteins in HT, relative to NT, was much less than those observed with NOX5. Thus, we demonstrate, for the first time, that NOX5 is expressed in human RPT cells and to greater extent than the other Nox isoforms in HT than NT. We suggest that the increased expression of NOX5, which may be responsible for the increased oxidative stress in RPT cells in human essential hypertension, is caused, in part, by a defective renal dopaminergic system. SN - 2213-2317 UR - https://www.unboundmedicine.com/medline/citation/24688893/Unique_role_of_NADPH_oxidase_5_in_oxidative_stress_in_human_renal_proximal_tubule_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-2317(14)00035-4 DB - PRIME DP - Unbound Medicine ER -