ArticleThe Journal of biological chemistry2008
Nox4 NAD(P)H oxidase mediates Src-dependent tyrosine phosphorylation of PDK-1 in response to angiotensin II: role in mesangial cell hypertrophy and fibronectin expression.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 130 citations in OpenAlex.
- Article
- Advance in Iron Metabolism, Oxidative Stress and Cellular Dysfunction in Experimental and Human Kidney Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- A Putative Role for TRPC6 in Immune-Mediated Kidney Injury.International journal of molecular sciences · 2023Review
- Nox4 as a novel therapeutic target for diabetic vascular complications.Redox biology · 2023Review
- Role of c-Src and reactive oxygen species in cardiovascular diseases.Molecular genetics and genomics : MGG · 2023Review
- Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- NOX4 MediatesAntioxidants (Basel, Switzerland) · 2021Article
- Molecular Mechanisms in Early Diabetic Kidney Disease: Glomerular Endothelial Cell Dysfunction.International journal of molecular sciences · 2020Review
- The renal antioxidative effect of losartan involves heat shock protein 70 in proximal tubule cells.Cell stress & chaperones · 2020Review
- CSF-1 in Osteocytes Inhibits Nox4-mediated Oxidative Stress and Promotes Normal Bone Homeostasis.JBMR plus · 2020Article
- Effects of a Red Orange and Lemon Extract in Obese Diabetic Zucker Rats: Role of Nicotinamide Adenine Dinucleotide Phosphate Oxidase.Journal of clinical medicine · 2020Article
- Redox regulation of tyrosine kinase signalling: more than meets the eye.Journal of biochemistry · 2020Review
- Angiotensin II-induced superoxide and decreased glutathione in proximal tubules: effect of dietary fructose.American journal of physiology. Renal physiology · 2020Article
- Tubular NOX4 expression decreases in chronic kidney disease but does not modify fibrosis evolution.Redox biology · 2019Article
- Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling.Bioscience reports · 2019Article
- Carcinogenesis and Reactive Oxygen Species Signaling: Interaction of the NADPH Oxidase NOX1-5 and Superoxide Dismutase 1-3 Signal Transduction Pathways.Antioxidants & redox signaling · 2019Review
- The novel NADPH oxidase 4 selective inhibitor GLX7013114 counteracts human islet cell death in vitro.PloS one · 2018Article
- The metabolic syndrome and chronic kidney disease.Translational research : the journal of laboratory and clinical medicine · 2017Review
- Diabetes and Kidney Disease: Role of Oxidative Stress.Antioxidants & redox signaling · 2016Review
- Oxidant Mechanisms in Renal Injury and Disease.Antioxidants & redox signaling · 2016Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of glomerular mesangial cells (MCs) by angiotensin II (Ang II) leads to hypertrophy and extracellular matrix accumulation. Here, we demonstrate that, in MCs, Ang II induces an increase in PDK-1 (3-phosphoinositide-dependent protein kinase-1) kinase activity that required its phosphorylation on tyrosine 9 and 373/376. Introduction into the cells of PDK-1, mutated on these tyrosine residues or kinase-inactive, attenuates Ang II-induced hypertrophy and fibronectin accumulation. Ang II-mediated PDK-1 activation and tyrosine phosphorylation (total and on residues 9 and 373/376) are inhibited in cells transfected with small interfering RNA for Src, indicating that Src is upstream of PDK-1. In cells expressing oxidation-resistant Src mutant C487A, Ang II-induced hypertrophy and fibronectin expression are prevented, suggesting that the pathway is redox-sensitive. Ang II also up-regulates Nox4 protein, and siNox4 abrogates the Ang II-induced increase in intracellular reactive oxygen species (ROS) generation. Small interfering RNA for Nox4 also inhibits Ang II-induced activation of Src and PDK-1 tyrosine phosphorylation (total and on residues 9 and 373/376), demonstrating that Nox4 functions upstream of Src and PDK-1. Importantly, inhibition of Nox4, Src, or PDK-1 prevents the stimulatory effect of Ang II on fibronectin accumulation and cell hypertrophy. This work provides the first evidence that Nox4-derived ROS are responsible for Ang II-induced PDK-1 tyrosine phosphorylation and activation through stimulation of Src. Importantly, this pathway contributes to Ang II-induced MC hypertrophy and fibronectin accumulation. These data shed light on molecular processes underlying the oxidative signaling cascade engaged by Ang II and identify potential targets for intervention to prevent renal hypertrophy and fibrosis.
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