PMID- 11912248
OWN - NLM
STAT- MEDLINE
DCOM- 20020819
LR  - 20210513
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 13
IP  - 4
DP  - 2002 Apr
TI  - Role of high glucose-induced nuclear factor-kappaB activation in monocyte 
      chemoattractant protein-1 expression by mesangial cells.
PG  - 894-902
LID - 10.1681/ASN.V134894 [doi]
AB  - Although high glucose (HG) has been shown to induce nuclear factor-kappaB 
      (NF-kappaB) activation in vascular cells, the upstream regulation and the 
      biologic significance of NF-kappaB activation in diabetic renal injury are not 
      clear. It was, therefore, examined if HG-induced generation of reactive oxygen 
      species (ROS) and protein kinase C (PKC) activation are involved in NF-kappaB 
      activation in mesangial cells (MC), and the role of NF-kappaB activation in 
      HG-induced monocyte chemoattractant protein-1 (MCP-1) expression by MC was 
      further investigated. Recent observations suggest that MCP-1 may play a role in 
      the development and progression of diabetic nephropathy. HG rapidly induced 
      NF-kappaB activation in MC as estimated by electrophoretic mobility shift assay. 
      Supershift assay suggests that most of the binding activity arose from p50/p50 
      and p50/p65 dimers. Antioxidants, pyrrolidine dithiocarbamate, 
      N-acetyl-L-cystein, and trolox effectively inhibited HG-induced NF-kappaB 
      activation in MC. HG rapidly generated dichlorofluorescin-sensitive intracellular 
      ROS in MC as measured by laser-scanning confocal microscopy. HG also activated 
      PKC rapidly in MC. Inhibition of PKC effectively blocked HG-induced intracellular 
      ROS generation and NF-kappaB activation in MC. HG increased MCP-1 mRNA expression 
      by 1.9-fold and protein secretion by 1.6-fold that of control glucose in MC 
      transfected with control vector but not in MC transfected with dominant negative 
      mutant inhibitor of NF-kappaB (IkappaBalphaM). Inhibition of either PKC or ROS 
      effectively blocked HG-induced, but not basal, MCP-1 protein secretion by MC 
      transfected with control vector. Thus this study demonstrates that HG rapidly 
      activates NF-kappaB in MC through PKC and ROS and suggests that HG-induced 
      NF-kappaB activation in MC may play a role in diabetic renal injury through 
      upregulation of MCP-1 mRNA and protein expression.
FAU - Ha, Hunjoo
AU  - Ha H
AD  - *Hyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea; and 
      daggerUniversity College London Medical School, The Rayne Institute, London, United 
      Kingdom.
FAU - Yu, Mi Ra
AU  - Yu MR
AD  - *Hyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea; and 
      daggerUniversity College London Medical School, The Rayne Institute, London, United 
      Kingdom.
FAU - Choi, Yoon Jin
AU  - Choi YJ
AD  - *Hyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea; and 
      daggerUniversity College London Medical School, The Rayne Institute, London, United 
      Kingdom.
FAU - Kitamura, Masanori
AU  - Kitamura M
AD  - *Hyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea; and 
      daggerUniversity College London Medical School, The Rayne Institute, London, United 
      Kingdom.
FAU - Lee, Hi Bahl
AU  - Lee HB
AD  - *Hyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea; and 
      daggerUniversity College London Medical School, The Rayne Institute, London, United 
      Kingdom.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Antioxidants)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Glomerular Mesangium/cytology/drug effects/*metabolism
MH  - Glucose/*administration & dosage/pharmacology
MH  - Intracellular Membranes/metabolism
MH  - Mice
MH  - NF-kappa B/*physiology
MH  - Protein Kinase C/antagonists & inhibitors/physiology
MH  - RNA, Messenger/metabolism
MH  - Reactive Oxygen Species/metabolism
EDAT- 2002/03/26 10:00
MHDA- 2002/08/20 10:01
CRDT- 2002/03/26 10:00
PHST- 2002/03/26 10:00 [pubmed]
PHST- 2002/08/20 10:01 [medline]
PHST- 2002/03/26 10:00 [entrez]
AID - 13/4/894 [pii]
AID - 10.1681/ASN.V134894 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2002 Apr;13(4):894-902. doi: 10.1681/ASN.V134894.