ArticleAmerican journal of physiology. Renal physiology2010
Rac1 mediates NaCl-induced superoxide generation in the thick ascending limb.
Article in American journal of physiology. Renal physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Reactive Oxygen Species (ROS) in Metabolic Disease-Don't Shoot the Metabolic Messenger.International journal of molecular sciences · 2025Review
- Angiotensin II-stimulated proximal nephron superoxide production and fructose-induced salt-sensitive hypertension.American journal of physiology. Renal physiology · 2024Article
- Importance of Micromilieu for Pathophysiologic Mineralocorticoid Receptor Activity-When the Mineralocorticoid Receptor Resides in the Wrong Neighborhood.International journal of molecular sciences · 2022Review
- The renal antioxidative effect of losartan involves heat shock protein 70 in proximal tubule cells.Cell stress & chaperones · 2020Review
- Stretch-Induced Increases in Intracellular Ca Stimulate Thick Ascending Limb OHypertension (Dallas, Tex. : 1979) · 2020Article
- Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension.Physiological reviews · 2019Review
- Biomarkers for Chronic Kidney Disease Associated with High Salt Intake.International journal of molecular sciences · 2017Review
- Organic compounds present in airborne particles stimulate superoxide production and DNA fragmentation: role of NOX and xanthine oxidase in animal tissues.Environmental science and pollution research international · 2016Article
- Angiotensin II stimulates superoxide production by nitric oxide synthase in thick ascending limbs.Physiological reports · 2016Article
- NADPH oxidases, reactive oxygen species, and the kidney: friend and foe.Journal of the American Society of Nephrology : JASN · 2013Review
- Anandamide inhibits transport-related oxygen consumption in the loop of Henle by activating CB1 receptors.American journal of physiology. Renal physiology · 2013Article
- Role of Rac1-mineralocorticoid-receptor signalling in renal and cardiac disease.Nature reviews. Nephrology · 2013Review
- Angiotensin II stimulates superoxide production in the thick ascending limb by activating NOX4.American journal of physiology. Cell physiology · 2012Article
- Water restriction increases renal inner medullary manganese superoxide dismutase (MnSOD).American journal of physiology. Renal physiology · 2012Article
- Selective Rac1 inhibition protects renal tubular epithelial cells from oxalate-induced NADPH oxidase-mediated oxidative cell injury.Urological research · 2012Article
- Angiotensin II- and salt-induced kidney injury through Rac1-mediated mineralocorticoid receptor activation.Journal of the American Society of Nephrology : JASN · 2012Article
- Epidermal growth factor-mediated proliferation and sodium transport in normal and PKD epithelial cells.Biochimica et biophysica acta · 2011Review
- NAD(P)H oxidase and renal epithelial ion transport.American journal of physiology. Regulatory, integrative and comparative physiology · 2011Review
- Angiotensin II stimulates thick ascending limb superoxide production via protein kinase C(α)-dependent NADPH oxidase activation.The Journal of biological chemistry · 2010Article
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2 authors at 2 institutions in 1 country.
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Abstract
Superoxide (O(2)(-)) produced by NADPH oxidase regulates Na absorption and renal hemodynamics. Increased NaCl in the thick ascending limb (TAL) stimulates O(2)(-) generation. However, we do not know whether physiological changes in NaCl concentration augment O(2)(-) generation, nor do we know the mediator(s) involved. In other cells, Rac1, a regulatory subunit of NADPH oxidase, is activated by elevated NaCl. We hypothesized that increasing luminal NaCl within the physiological range activates Rac1 and NADPH oxidase and, thereby, increases O(2)(-) production. We increased NaCl from 10 to 57 mM in medullary TAL suspensions and used lucigenin to measure O(2)(-) generation and Western blot to measure Rac1 activity. Increasing NaCl stimulated O(2)(-) generation from 1.41 +/- 0.16 to 2.71 +/- 0.30 nmol O(2)(-) x min(-1) x mg protein(-1) (n = 6, P < 0.05). This increase was blocked by the Na-K-2Cl cotransporter inhibitor furosemide and the NADPH oxidase inhibitor apocynin. To examine the role of Rac1 in NaCl-induced O(2)(-) production, we measured Rac1 translocation by Western blot. When we added NaCl, Rac1 in the particulate fraction increased from 6.8 +/- 0.8 to 11.7 +/- 2.4% of total Rac1 (n = 7, P < 0.05). Then we measured O(2)(-) generation in the presence and absence of the Rac1 inhibitor. In the absence of the Rac1 inhibitor, NaCl increased O(2)(-) generation from 1.07 +/- 0.24 to 2.02 +/- 0.49 nmol O(2)(-) x min(-1) x mg protein(-1), and this increase was completely blocked by the inhibitor. Similarly, in vivo treatment of TALs with adenovirus expressing dominant-negative Rac1 decreased NaCl-induced O(2)(-) generation by 60% compared with control (0.33 +/- 0.04 vs. 0.81 +/- 0.17 nmol O(2)(-) x min(-1) x mg protein(-1), n = 6, P < 0.05). We concluded that physiological increases in NaCl stimulate TAL O(2)(-) generation by activating Rac1.
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