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


CONCLUSIONS
Increased ROS in podocytes may play a role in the pathogenesis of podocyte injury in diabetic nephropathy.
Department of Internal Medicine and Clinical Research Institute, Soon Chun Hyang University Cheonan Hospital, Cheonan, Korea.
Eun-Young
EY
Lee
Choon Hee
CH
Chung
Jung Hyun
JH
Kim
Hea-Jung
HJ
Joung
Sae Yong
SY
Hong
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000473:pathology; D005947:Glucose / Q000494:pharmacology; D051379:Mice; D050199:Podocytes / Q000473:pathology*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D011493:Protein Kinase C; D005947:Glucose