Journal Article

Antioxidants ameliorate the expression of vascular endothelial growth factor mediated by protein kinase C in diabetic podocytes

Eun-Young Lee, Choon Hee Chung, Jung Hyun Kim, Hea-Jung Joung and Sae Yong Hong

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 21, issue 6, pages 1496-1503
Published in print June 2006 | ISSN: 0931-0509
Published online February 2006 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfl022
Antioxidants ameliorate the expression of vascular endothelial growth factor mediated by protein kinase C in diabetic podocytes

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Background. The increased production of reactive oxygen species (ROS) may be involved in the onset or development of diabetic vascular complications. The release of ROS from podocytes plays a role in the pathogenesis of glomerular damage in various experimental glomerular diseases. Although it is assumed that the podocyte injury also plays an important role in diabetic nephropathy, the mechanism is still unknown.

Methods. Using a differentiated mouse podocyte cell line, we investigated: (1) whether a high level of ambient glucose increases the level of ROS, (2) whether the protein kinase C (PKC) pathway is involved in a high-glucose-induced generation of ROS and vascular endothelial growth factor (VEGF) and (3) whether antioxidants ameliorate PKC-mediated VEGF expression in diabetic milieu.

Results. Intracellular ROS generation was significantly higher in high glucose than in control conditions in cultured podocytes. High ambient glucose also increased VEGF mRNA and protein expression. The high-glucose-induced increases in ROS and VEGF mRNA and protein by podocytes were effectively inhibited by pretreatment with various antioxidants and were completely restored by PKC inhibition. The results show that cultured mouse podocytes produce ROS in response to high glucose, and that PKC is involved in high-glucose-induced ROS and VEGF production by podocyte.

Conclusion. Increased ROS in podocytes may play a role in the pathogenesis of podocyte injury in diabetic nephropathy.

Keywords: antioxidant; diabetic nephropathy; podocyte; protein kinase C; reactive oxygen species

Journal Article.  4770 words.  Illustrated.

Subjects: Nephrology

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