NOX-mediated impairment of PDGF-induced DNA synthesis in peripheral blood lymphocytes of children with idiopathic nephrotic syndrome.

Abstract

BackgroundCellular oxidative stress, inflammatory responses, and immunogenic events are involved in pathogenesis of idiopathic nephrotic syndrome (INS); however, the exact mechanism remains unknown. We examined NADPH oxidase (NOX) activity and platelet-derived growth factor (PDGF)-induced DNA synthesis in peripheral blood lymphocytes (PBL) of patients with INS.MethodsPBL from 15 patients with INS and 15 age- and gender-matched controls were isolated, and enzyme activities of NOX, catalase, and superoxide dismutase (SOD) were measured along with the assay of malondialdehyde levels and bromo-deoxyuridine incorporation. Protein expression of NOX-1 was measured using western blot analysis.ResultsPatients with INS had significantly (P<0.01) higher NOX activity and increased protein expression of NOX-1 in PBL as compared with controls. Catalase and SOD activities were markedly lower with lipid peroxide levels significantly (P<0.01) increased in patients with INS. Ex vivo DNA synthesis in PDGF-stimulated PBL was significantly (P<0.01) reduced in patients with INS; however, diphenyliodonium, an inhibitor of NOX, markedly corrected impairment in growth factor-induced BrdU incorporation.ConclusionsThese results show that NOX activation might have a role in regulation of lymphocytic activity in patients with INS through the impairment of PDGF mitogenic function and might contribute toward pathogenesis of nephrotic syndrome.

• Authors: Amal Al-Eisa, Gursev S Dhaunsi
• Journal: Pediatric research (Pediatr Res) Vol. 82 Issue 4 Pg. 629-633 (Oct 2017) ISSN: 1530-0447 [Electronic] United States
• PMID: 28613279 (Publication Type: Journal Article)

Chemical References

• Lipid Peroxides
• Platelet-Derived Growth Factor
• Malondialdehyde
• Catalase
• Superoxide Dismutase
• NADPH Oxidase 1
• NOX1 protein, human

Topics

• Case-Control Studies
• Catalase (blood)
• Cells, Cultured
• Child
• Child, Preschool
• DNA Replication (drug effects)
• Enzyme Activation
• Female
• Humans
• Lipid Peroxidation (drug effects)
• Lipid Peroxides (blood)
• Lymphocytes (drug effects, enzymology)
• Male
• Malondialdehyde (blood)
• NADPH Oxidase 1 (blood)
• Nephrotic Syndrome (blood, diagnosis, enzymology)
• Oxidative Stress (drug effects)
• Platelet-Derived Growth Factor (pharmacology)
• Superoxide Dismutase (blood)