High levels of serum free fatty acids (FFAs) are associated with lipotoxicity and type 2 diabetes. Palmitic acid (PA) is the predominant circulating saturated FFA. PA induces mitochondrial superoxide and hydrogen peroxide (H2 O 2 ) generation in cultured podocytes. To elucidate the role of PA in antioxidant defense systems in diabetic nephropathy (DN), cultured podocytes were exposed to 250 μM PA for 1-24 hr, and protein expressions of catalase, peroxiredoxins (Prxs), and glutathione peroxidase (GPx) were examined by western blot analysis. PA induced an early transient increase in the Prx1, Prx2, and GPx1 levels in podocytes, but not catalase. Long-term exposure of PA to podocytes significantly decreased the protein levels of Prx1, Prx2, GPx1, and catalase. Coincubation of PA-treated cells with oleic acid, however, restored the expression of these proteins. In advanced human diabetic glomeruli, H2 O2 generation was elevated as shown by increased fluorescence of dichlorofluorescein. Strong immunostaining for Prx1, Prx2, GPx1, and catalase was observed in the podocytes of advanced human DN, wherein transforming growth factor-β1 staining was also positive. These results suggest that podocytes are susceptible to PA-induced oxidative damage with impaired peroxidase activity and that peroxidases have futile antioxidant effects in the podocytes in the late stages of DN. Given this, PA-induced podocyte injury via inadequate peroxidase response to H2 O2 appears to play an important role in the pathogenesis of DN.
Pubmed ID: 30132841 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
An Antibody supplier; Dako was purchased by Agilent in 2012 and several years later the websites began to reflect the Dako products as part of the Agilent catalog.
View all literature mentionsThis unknown targets Peroxiredoxin 2 (Prx2)
View all literature mentionsThis unknown targets GPX1
View all literature mentionsThis polyclonal secondary targets IgG F(ab')2
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis unknown targets Catalase
View all literature mentionsThis monoclonal targets beta Actin Loading Control
View all literature mentionsThis unknown targets PRDX1
View all literature mentions