PMID- 17977907
OWN - NLM
STAT- MEDLINE
DCOM- 20080304
LR  - 20131121
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 294
IP  - 1
DP  - 2008 Jan
TI  - Homocysteine stimulates monocyte chemoattractant protein-1 expression in the 
      kidney via nuclear factor-kappaB activation.
PG  - F236-44
AB  - Hyperhomocysteinemia, or an elevation of blood homocysteine (Hcy) levels, is 
      associated with cardiovascular disorders. Although kidney dysfunction is an 
      important risk factor causing hyperhomocysteinemia, the direct effect of Hcy on 
      the kidney is not well documented. There is a positive association between an 
      elevation of blood Hcy levels and the development of chronic kidney disease. 
      Inflammatory response such as increased chemokine expression has been implicated 
      as one of the mechanisms for renal disease. Monocyte chemoattractant protein-1 
      (MCP-1) is a potent chemokine that is involved in the inflammatory response in 
      renal disease. Nuclear factor-kappaB (NF-kappaB) plays an important role in 
      upregulation of MCP-1 expression. We investigated the effect of 
      hyperhomocysteinemia on MCP-1 expression and the molecular mechanism underlining 
      such an effect in rat kidneys as well as in proximal tubular cells. 
      Hyperhomocysteinemia was induced in rats fed a high-methionine diet for 12 wk. 
      The MCP-1 mRNA expression and MCP-1 protein levels were significantly increased 
      in kidneys isolated from hyperhomocysteinemic rats. The NF-kappaB activity was 
      significantly increased in the same kidneys. Pretreatment of hyperhomocysteinemic 
      rats with a NF-kappaB inhibitor abolished hyperhomocysteinemia-induced MCP-1 
      expression in the kidney. To confirm the causative role of NF-kappaB activation 
      in MCP-1 expression, human kidney proximal tubular cells were transfected with 
      decoy NF-kappaB oligodeoxynucleotide to inhibit NF-kappaB activation. Such a 
      treatment prevented Hcy-induced MCP-1 mRNA expression in tubular cells. Our 
      results suggest that hyperhomocysteinemia stimulates MCP-1 expression in the 
      kidney via NF-kappaB activation. Such an inflammatory response may contribute to 
      renal injury associated with hyperhomocysteinemia.
FAU - Hwang, Sun-Young
AU  - Hwang SY
AD  - Department of Animal Science, University of Manitoba, Winnipeg, Canada.
FAU - Woo, Connie W H
AU  - Woo CW
FAU - Au-Yeung, Kathy K W
AU  - Au-Yeung KK
FAU - Siow, Yaw L
AU  - Siow YL
FAU - Zhu, Tong Y
AU  - Zhu TY
FAU - O, Karmin
AU  - O K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071031
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (CCL2 protein, human)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Homocysteine/*metabolism/pharmacology
MH  - Humans
MH  - Hyperhomocysteinemia/chemically induced/metabolism/pathology
MH  - Kidney/*metabolism/pathology
MH  - Kidney Tubules, Proximal/*metabolism/pathology
MH  - Male
MH  - Methionine
MH  - NF-kappa B/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2007/11/06 09:00
MHDA- 2008/03/05 09:00
CRDT- 2007/11/06 09:00
PHST- 2007/11/06 09:00 [pubmed]
PHST- 2008/03/05 09:00 [medline]
PHST- 2007/11/06 09:00 [entrez]
AID - 00331.2007 [pii]
AID - 10.1152/ajprenal.00331.2007 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2008 Jan;294(1):F236-44. doi: 
      10.1152/ajprenal.00331.2007. Epub 2007 Oct 31.