PMID- 18418435
OWN - NLM
STAT- MEDLINE
DCOM- 20080612
LR  - 20181201
IS  - 0008-4212 (Print)
IS  - 0008-4212 (Linking)
VI  - 86
IP  - 3
DP  - 2008 Mar
TI  - Homocysteine stimulates monocyte chemoattractant protein-1 expression in 
      mesangial cells via NF-kappaB activation.
PG  - 88-96
LID - 10.1139/y08-002 [doi]
AB  - Hyperhomocysteinemia is regarded as an independent risk factor for cardiovascular 
      disorders. Although renal dysfunction or failure is one of the important factors 
      causing hyperhomocysteinemia, the role of homocysteine (Hcy) in the development 
      of glomerulosclerosis is largely unknown. One of the key events in the 
      pathogenesis of glomerulosclerosis is the infiltration of circulating monocytes 
      into affected glomeruli. The objective of the present study was to investigate 
      the effect of Hcy on the expression of monocyte chemoattractant protein-1 (MCP-1) 
      in kidney mesangial cells and the mechanisms involved. Levels of MCP-1 and mRNA 
      were significantly elevated in Hcy-treated rat mesangial cells. This increase was 
      associated with activation of NF-kappaB as a result of increased phosphorylation 
      of the inhibitor protein IkappaBalpha. Monocyte chemotactic activity in these 
      cells was also enhanced. In addition, there was a significant elevation of 
      superoxide anion produced by Hcy-treated cells, which preceded the increased 
      phosphorylation of IkappaBalpha. Addition of superoxide dismutase or NF-kappaB 
      inhibitors to the culture medium abolished Hcy-induced NF-kappaB activation and 
      MCP-1 expression. Taken together, these results indicate that Hcy induced MCP-1 
      expression in mesangial cells. Such a process was mediated by oxidative stress 
      and NF-kappaB activation. This may further aggravate renal function in patients 
      with hyperhomocysteinemia.
FAU - Cheung, Giselle T Y
AU  - Cheung GT
AD  - Department of Animal Science, University of Manitoba, Integrative Biology 
      Laboratory, St. Boniface Hospital Research Centre, Winnipeg, MB R2H2A6, Canada.
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  - Canada
TA  - Can J Physiol Pharmacol
JT  - Canadian journal of physiology and pharmacology
JID - 0372712
RN  - 0 (Chemokine CCL2)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (NF-kappa B)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 11062-77-4 (Superoxides)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (polyethylene glycol-superoxide dismutase)
SB  - IM
MH  - Animals
MH  - Cell Movement/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Electrophoretic Mobility Shift Assay
MH  - Free Radical Scavengers/pharmacology
MH  - Homocysteine/*pharmacology
MH  - Male
MH  - Mesangial Cells/cytology/*drug effects/metabolism
MH  - Models, Biological
MH  - Monocytes/drug effects/physiology
MH  - NF-kappa B/*metabolism
MH  - Nuclear Proteins/metabolism
MH  - Oxidative Stress/drug effects
MH  - Phosphorylation/drug effects
MH  - Polyethylene Glycols/pharmacology
MH  - Protein Binding/drug effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Superoxide Dismutase/pharmacology
MH  - Superoxides/metabolism
EDAT- 2008/04/18 09:00
MHDA- 2008/06/13 09:00
CRDT- 2008/04/18 09:00
PHST- 2008/04/18 09:00 [pubmed]
PHST- 2008/06/13 09:00 [medline]
PHST- 2008/04/18 09:00 [entrez]
AID - y08-002 [pii]
AID - 10.1139/y08-002 [doi]
PST - ppublish
SO  - Can J Physiol Pharmacol. 2008 Mar;86(3):88-96. doi: 10.1139/y08-002.