NDT Advance Access published online on February 16, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl022
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1 Department of Internal Medicine and Clinical Research Institute, Soon Chun Hyang University Cheonan Hospital, Cheonan, Korea
* To whom correspondence should be addressed. 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.
Received April 13, 2005
Accepted January 17, 2006
Original Article
Antioxidants ameliorate the expression of vascular endothelial growth factor mediated by protein kinase C in diabetic podocytes
Eun-Young Lee 1,
Choon Hee Chung 2 *,
Jung Hyun Kim 1,
Hea-Jung Joung 3,
and
Sae Yong Hong 1
2 Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
3 System Application and Development Team, Bioneer Corporation, Daejeon, Korea
Choon Hee Chung, E-mail: cchung{at}yonsei.ac.kr
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