PMID- 12234286
OWN - NLM
STAT- MEDLINE
DCOM- 20030225
LR  - 20161124
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 62
IP  - 4
DP  - 2002 Oct
TI  - Enhanced MCP-1 expression during ischemia/reperfusion injury is mediated by 
      oxidative stress and NF-kappaB.
PG  - 1160-70
AB  - BACKGROUND: Renal ischemia/reperfusion injury is a major cause of acute renal 
      failure in both native kidneys and renal allografts. One important feature of 
      such injury is monocyte/macrophage infiltration into the renal tissue. The 
      infiltration of monocytes/macrophages can be induced by chemotactic factors 
      produced by renal cells. Monocyte chemoattractant protein-1 (MCP-1) is a potent 
      chemoattractant protein for monocyte recruitment. The objective of the present 
      study was to investigate mechanisms of elevated MCP-1 expression in rat kidney 
      during ischemia/reperfusion injury. METHODS: The left kidney was subjected to one 
      hour of ischemia followed by reperfusion for various time periods. The expression 
      of MCP-1 mRNA was determined by nuclease protection assay and MCP-1 protein was 
      identified by immunohistochemistry. Activation of a nuclear factor-kappa B 
      (NF-kappaB) was determined by electrophoretic mobility shift assay and the level 
      of lipid peroxides in the kidney was measured. RESULTS: There was a significant 
      increase in MCP-1 expression in the ischemia/reperfusion kidney 2 hours after 
      reperfusion (210% of the control). This increase was accompanied by activation of 
      NF-kappaB, suggesting that this transcription factor might be involved in the 
      event. The number of monocytes was significantly elevated in the kidney 3 days 
      after ischemia/reperfusion. Pretreatment of rats with NF-kappaB inhibitors not 
      only prevented NF-kappaB activation induced by ischemia/reperfusion, but also 
      inhibited MCP-1 mRNA expression. Further analysis revealed that oxidative stress 
      and increased IkappaB-alpha phosphorylation might be an underlying mechanism for 
      NF-kappaB activation and subsequent MCP-1 mRNA expression in the 
      ischemia/reperfusion kidney. CONCLUSION: The present study clearly demonstrates 
      that enhanced MCP-1 expression in rat kidney during ischemia/reperfusion injury 
      is mediated by NF-kappaB activation and oxidative stress. Elevated MCP-1 
      expression might be responsible for increased monocyte infiltration in the 
      injured kidney.
FAU - Sung, Fion L
AU  - Sung FL
AD  - Department of Pharmacology, Faculty of Medicine, University of Hong Kong, 21 
      Sassoon Road, Pokfulam, Hong Kong, PR China.
FAU - Zhu, Tong Y
AU  - Zhu TY
FAU - Au-Yeung, Kathy K W
AU  - Au-Yeung KK
FAU - Siow, Yaw L
AU  - Siow YL
FAU - O, Karmin
AU  - O K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Chemokine CCL2)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfkbia protein, rat)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/*genetics
MH  - Gene Expression/physiology
MH  - I-kappa B Proteins/genetics
MH  - Kidney/cytology/metabolism
MH  - Lipid Peroxidation/physiology
MH  - Male
MH  - Monocytes/cytology
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/*metabolism
MH  - Neutrophils/cytology
MH  - Oxidative Stress/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/*metabolism/*physiopathology
EDAT- 2002/09/18 10:00
MHDA- 2003/02/26 04:00
CRDT- 2002/09/18 10:00
PHST- 2002/09/18 10:00 [pubmed]
PHST- 2003/02/26 04:00 [medline]
PHST- 2002/09/18 10:00 [entrez]
AID - S0085-2538(15)48658-2 [pii]
AID - 10.1111/j.1523-1755.2002.kid577.x [doi]
PST - ppublish
SO  - Kidney Int. 2002 Oct;62(4):1160-70. doi: 10.1111/j.1523-1755.2002.kid577.x.