ArticleAntioxidants & redox signaling2014
Hydrogen sulfide targets EGFR Cys797/Cys798 residues to induce Na(+)/K(+)-ATPase endocytosis and inhibition in renal tubular epithelial cells and increase sodium excretion in chronic salt-loaded rats.
Article in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 58 citations in OpenAlex.
- Possible Links Between PMInternational journal of molecular sciences · 2026Review
- Early-Life Hydrogen Sulfide Signaling as a Target for Cardiovascular-Kidney-Metabolic Syndrome Reprogramming.Antioxidants (Basel, Switzerland) · 2025Review
- Chemoprotective Mechanism of Sodium Thiosulfate Against Cisplatin-Induced Nephrotoxicity Is via Renal Hydrogen Sulfide, Arginine/cAMP and NO/cGMP Signaling Pathways.International journal of molecular sciences · 2025Article
- Complex Pathophysiology of Acute Kidney Injury (AKI) in Aging: Epigenetic Regulation, Matrix Remodeling, and the Healing Effects of HBiomolecules · 2024Review
- Static Cold Storage with Mitochondria-Targeted Hydrogen Sulfide Donor Improves Renal Graft Function in an Ex Vivo Porcine Model of Controlled Donation-after-Cardiac-Death Kidney Transplantation.International journal of molecular sciences · 2023Article
- Hydrogen sulfide-induced post-translational modification as a potential drug target.Genes & diseases · 2023Review
- Hydrogen Sulfide Biomedical Research in China-20 Years of Hindsight.Antioxidants (Basel, Switzerland) · 2022Review
- Recent Development of the Molecular and Cellular Mechanisms of Hydrogen Sulfide Gasotransmitter.Antioxidants (Basel, Switzerland) · 2022Review
- Hydrogen Sulfide Alleviates Manganese Stress inInternational journal of molecular sciences · 2022Article
- Possible molecular basis of the biochemical effects of cysteine-derived persulfides.Frontiers in molecular biosciences · 2022Review
- The role of sulfur compounds in chronic obstructive pulmonary disease.Frontiers in molecular biosciences · 2022Review
- Extracellular cysteines C226 and C232 mediate hydrogen sulfide-dependent inhibition of Orai3-mediated store-operated calcium entry.American journal of physiology. Cell physiology · 2022Article
- Protective effect of hydrogen sulfide on the kidney (Review).Molecular medicine reports · 2021Review
- Mitochondrial Redox Signaling and Oxidative Stress in Kidney Diseases.Biomolecules · 2021Review
- Spatiotemporal regulation of hydrogen sulfide signaling in the kidney.Redox biology · 2021Review
- The Antiviral Roles of Hydrogen Sulfide by Blocking the Interaction between SARS-CoV-2 and Its Potential Cell Surface Receptors.Oxidative medicine and cellular longevity · 2021Review
- Hydrogen Sulfide and the Kidney.Advances in experimental medicine and biology · 2021Article
- Conformational Insight on WT- and Mutated-EGFR Receptor Activation and Inhibition by Epigallocatechin-3-Gallate: Over a Rational Basis for the Design of Selective Non-Small-Cell Lung Anticancer Agents.International journal of molecular sciences · 2020Article
- Hydrogen Sulfide: Recent Progression and Perspectives for the Treatment of Diabetic Nephropathy.Molecules (Basel, Switzerland) · 2019Review
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Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe role of hydrogen sulfide (H2S) in renal sodium and water homeostasis is unknown. We investigated whether H2S promoted Na(+)/K(+)-ATPase endocytosis via the H2S/EGFR/gab1/PI3K/Akt pathway in renal tubular epithelial cells.
resultsH2S decreased Na(+)/K(+)-ATPase activity and induced its endocytosis in renal tubular epithelial cells, which was abrogated by small interfering RNA (siRNA) knockdown of epidermal growth factor receptor (EGFR) and gab1, a dominant-negative mutant of Akt and PI3K inhibitors. H2S increased EGFR, gab1, PI3K, and Akt phosphorylation in both renal tubular epithelial cells and kidneys of chronic salt-loaded rats. These increases were abrogated by siRNA knockdown of EGFR, but not of c-Src. Radiolabeled H2S exhibited transient, direct binding to EGFR and directly activated EGFR. Some disulfide bonds in EGFR intracellular kinase domain were susceptible to H2S-induced cleavage. Mutations of EGFR Cys797 (human) or Cys798 (rat) residues increased EGFR activity and prevented H2S-induced Na(+)/K(+)-ATPase endocytosis. H2S also inhibited sodium hydrogen exchanger-3 (NHE3) activity in renal tubular epithelial cells. H2S treatment increased sodium excretion in chronic and acute salt-loaded rats and decreased blood pressure in chronic salt-loaded rats. INNOVATION AND
conclusionH2S directly targets some disulfide bonds in EGFR, which activates the EGFR/gab1/PI3K/Akt pathway and subsequent Na(+)/K(+)-ATPase endocytosis and inhibition in renal tubular epithelial cells. EGFR Cys797/Cys798 residues are essential for an intrinsic inhibitory mechanism and for H2S actions in renal tubular epithelial cells. Other pathways, including NHE3, may be involved in mediating the renal effects of H2S. Our results reveal a new renal sodium homeostasis mechanism, which may provide for novel treatment approaches for diseases related to renal sodium homeostasis dysfunction.
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