ArticleAmerican journal of physiology. Renal physiology2012
Novel signaling mechanisms of intracellular angiotensin II-induced NHE3 expression and activation in mouse proximal tubule cells.
Article in American journal of physiology. Renal physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- Na/K-ATPase in the renal proximal tubule cell: classic & novel roles in sodium handling.Frontiers in physiology · 2026Review
- Sex differences in the renin-angiotensin-aldosterone system and its roles in hypertension, cardiovascular, and kidney diseases.Frontiers in cardiovascular medicine · 2023Review
- Genetic Deletion of ATInternational journal of molecular sciences · 2022Article
- Angiotensin II and ATInternational journal of molecular sciences · 2022Review
- The NaFrontiers in physiology · 2022Review
- New Insights into the Critical Importance of Intratubular NaCurrent hypertension reports · 2021Review
- Evidence for a Physiological Mitochondrial Angiotensin II System in the Kidney Proximal Tubules: Novel Roles of Mitochondrial Ang II/ATHypertension (Dallas, Tex. : 1979) · 2020Article
- Sex difference in kidney electrolyte transport II: impact of KAmerican journal of physiology. Renal physiology · 2019Article
- Proximal Tubule-Specific Deletion of the NHE3 (NaHypertension (Dallas, Tex. : 1979) · 2019Article
- ERK1,2 Signalling Pathway along the Nephron and Its Role in Acid-base and Electrolytes Balance.International journal of molecular sciences · 2019Review
- EXPRESSION OF THE RENIN-ANGIOTENSIN SYSTEM COMPONENTS IN ONCOLOGIC DISEASES.Acta clinica Croatica · 2019Review
- Role of Thioredoxin 1 in Impaired Renal Sodium Excretion of hDJournal of the American Heart Association · 2019Article
- Genetic and genomic evidence for an important role of the NaPhysiological genomics · 2019Review
- Intratubular and intracellular renin-angiotensin system in the kidney: a unifying perspective in blood pressure control.Clinical science (London, England : 1979) · 2018Review
- Antenatal betamethasone attenuates the angiotensin-(1-7)-Mas receptor-nitric oxide axis in isolated proximal tubule cells.American journal of physiology. Renal physiology · 2017Article
- Angiotensinogen import in isolated proximal tubules: evidence for mitochondrial trafficking and uptake.American journal of physiology. Renal physiology · 2017Article
- Immunohistochemical expression of intrarenal renin angiotensin system components in response to tempol in rats fed a high salt diet.World journal of nephrology · 2017Article
- Recent Updates on the Proximal Tubule Renin-Angiotensin System in Angiotensin II-Dependent Hypertension.Current hypertension reports · 2016Review
- The NHERF1 PDZ1 domain and IRBIT interact and mediate the activation of Na+/H+ exchanger 3 by ANG II.American journal of physiology. Renal physiology · 2016Article
- Albuminuria enhances NHE3 and NCC via stimulation of mitochondrial oxidative stress/angiotensin II axis.Oncotarget · 2016Article
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Authors and funding
3 authors at 2 institutions in 1 country.
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Abstract
Expression of a cytosolic cyan fluorescent fusion protein of angiotensin II (ECFP/ANG II) in proximal tubules increases blood pressure in rodents. To determine cellular signaling pathways responsible for this response, we expressed ECFP/ANG II in transport-competent mouse proximal convoluted tubule cells (mPCT) from wild-type (WT) and type 1a ANG II receptor-deficient (AT(1a)-KO) mice and measured its effects on intracellular ANG II levels, surrogates of Na/H exchanger 3 (NHE3)-dependent Na(+) absorption, as well as MAP kinases and NF-κB signaling. In WT mPCT cells, ECFP/ANG II expression doubled ANG II levels, increased NHE3 expression and membrane phospho-NHE3 proteins threefold and intracellular Na(+) concentration by 65%. These responses were associated with threefold increases in phospho-ERK 1/2 and phospho-p38 MAPK, fivefold increases in p65 subunit of NF-κB, and threefold increases in phospho-IKKα/β (Ser 176/180) proteins. These signaling responses to ECFP/ANG II were inhibited by losartan (AT(1) blocker), PD123319 (AT(2) blocker), U0126 (MEK1/MEK2 inhibitor), and RO 106-9920 (NF-κB inhibitor). In mPCT cells of AT(1a)-KO mice, ECFP/ANG II also increased the levels of NHE3, p-ERK1/2, and p65 proteins above their controls, but considerably less so than in WT cells. In WT mice, selective expression of ECFP/ANG II in vivo in proximal tubules significantly increased blood pressure and indices of sodium reabsorption, in particular levels of phosphorylated NHE3 protein in the membrane fraction and proton gradient-stimulated (22)Na(+) uptake by proximal tubules. We conclude that intracellular ANG II may induce NHE3 expression and activation in mPCTs via AT(1a)- and AT(2) receptor-mediated activation of MAP kinases ERK 1/2 and NF-κB signaling pathways.
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