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Effects of inosine monophosphate dehydrogenase inhibition on high glucose-induced cellular reactive oxygen species in mesangial cells

Authors
 J.S. Song  ;  K.H. Huh  ;  J. Park  ;  M.K. Ju  ;  M.S. Kim  ;  Y.S. Kim 
Citation
 TRANSPLANTATION PROCEEDINGS, Vol.40(2) : 464-466, 2008 
Journal Title
 TRANSPLANTATION PROCEEDINGS 
ISSN
 0041-1345 
Issue Date
2008
MeSH
Animals ; Glomerular Mesangium/cytology ; Glomerular Mesangium/drug effects ; Glomerular Mesangium/physiology* ; Glucose/pharmacology* ; IMP Dehydrogenase/antagonists & inhibitors* ; IMP Dehydrogenase/genetics ; Mice ; Mice, Transgenic ; Mycophenolic Acid/pharmacology* ; RNA, Small Interfering/genetics ; Reactive Oxygen Species/metabolism*
Keywords
Animals ; Glomerular Mesangium/cytology ; Glomerular Mesangium/drug effects ; Glomerular Mesangium/physiology* ; Glucose/pharmacology* ; IMP Dehydrogenase/antagonists & inhibitors* ; IMP Dehydrogenase/genetics ; Mice ; Mice, Transgenic ; Mycophenolic Acid/pharmacology* ; RNA, Small Interfering/genetics ; Reactive Oxygen Species/metabolism*
Abstract
Mesangial cell extracellular matrix (ECM) synthesis plays an important role in chronic renal diseases including chronic renal allograft dysfunction and diabetic nephropathy. Although inosine monophosphate dehydrogenase 2 (IMPDH2), as a target of mycophenolic acid (MPA), is important for de novo guanosine synthesis in lymphocytes, mesenchymal cells are not wholly dependent on it. To explore the importance of IMPDH2 on the inhibitory effects of MPA in mesangial cells (MC), we compared the effects of MPA and IMPDH2 siRNA on high glucose (HG)-induced fibronectin secretion and cellular reactive oxygen species (ROS). Mouse mesangial cells (MMC) were stimulated with HG (30 mmol/L D-glucose) in the presence or absence of MPA pretreatment or IMPDH2 siRNA transfection. Fibronectin secretion was measured by Western blot analysis, and dichlorofluorescein (DCF)-sensitive cellular ROS assessed by flow cytometry. HG increased fibronectin secretion by 1.8-fold at 24 hours and DCF-sensitive cellular ROS by 1.5-fold at 1 hour. MPA at 10 micromol/L totally inhibited HG-induced fibronectin secretion and cellular ROS in MMC. However, IMPDH2 siRNA only partially suppressed HG-induced fibronectin secretion and cellular ROS. These results suggested that MPA may inhibit HG-induced fibronectin secretion partially through inhibiting cellular ROS and the inhibition of IMPDH2 may be partially involved in the mechanism of MPA.
Full Text
http://www.sciencedirect.com/science/article/pii/S0041134508000171
DOI
10.1016/j.transproceed.2008.01.016
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Soo(김명수) ORCID logo https://orcid.org/0000-0002-8975-8381
Kim, Yu Seun(김유선) ORCID logo https://orcid.org/0000-0002-5105-1567
Joo, Man Ki(주만기) ORCID logo https://orcid.org/0000-0002-4112-7003
Huh, Kyu Ha(허규하) ORCID logo https://orcid.org/0000-0003-1364-6989
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108102
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