Lipopolysaccharide induces inducible nitric oxide synthase-dependent podocyte dysfunction via a hypoxia-inducible factor 1α and cell division control protein 42 and Ras-related C3 botulinum toxin substrate 1 pathway

Free Radical Biology & Medicine
Ahmad K Mashmoushi, Jim C Oates

Abstract

Urine protein loss in immune complex-mediated diseases such as lupus nephritis is associated with podocyte foot process effacement (podocytopathy) but is not always dependent on glomerular immune complex deposition. Several murine and human studies have associated lupus nephritis with inducible nitric oxide synthase (iNOS) expression in what appear to be podocytes. This study was conducted to determine mechanisms of immune-complex-independent and iNOS-dependent podocyte dysfunction. Conditionally immortalized podocytes were cultured with lipopolysaccharide (LPS) and nitric oxide (NO), superoxide (SO), or peroxynitrite donors in the presence or absence of inhibitors of iNOS, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase or monocyte chemotactic protein 1 (MCP-1), or with sepiapterin to increase coupling of iNOS homodimers. Podocyte NO, SO, and MCP-1 production and nitrotyrosine modifications were determined. The podocytopathy phenotype was determined by measuring cell motility and membrane permeability to albumin. This study determined that NO produced by iNOS is sufficient and necessary to induce podocytopathy. NO probably induces this phenotype via hypoxia-inducible factor 1α and cell division control prot...Continue Reading

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Citations

Sep 19, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xiu ChenJin-Hai Tang
Apr 1, 2017·Nature Reviews. Rheumatology·Laurence Morel
Nov 28, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Walaa Yehia AbdelzaherMina Ezzat Attya
Nov 6, 2020·Cellular Signalling·Karl-Friedrich Beck, Josef Pfeilschifter
Aug 28, 2021·Cells·Maria Luísa da Silveira Hahmeyer, José Eduardo da Silva-Santos

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