PMID- 16845898
OWN - NLM
STAT- MEDLINE
DCOM- 20060823
LR  - 20171116
IS  - 0008-4212 (Print)
IS  - 0008-4212 (Linking)
VI  - 84
IP  - 1
DP  - 2006 Jan
TI  - Folic acid inhibits homocysteine-induced superoxide anion production and nuclear 
      factor kappa B activation in macrophages.
PG  - 141-7
AB  - Folic acid supplementation is a promising approach for patients with 
      cardiovascular diseases associated with hyperhomocysteinemia. We have 
      demonstrated that homocysteine (Hcy) activates nuclear factor-kappaB (NF-kappaB), 
      a transcription factor that plays an important role in inflammatory responses. 
      The aim of the present study was to investigate the effect of folic acid on 
      Hcy-induced NF-kappaB activation in macrophages. Hcy treatment (100 micromol/L) 
      resulted in NF-kappaB activation and increased monocyte chemoattractant protein-1 
      (MCP-1) expression in THP-1 derived macrophages. Hcy-induced NF-kappaB activation 
      was associated with a significant increase in the intracellular superoxide anion 
      levels. There was a significant increase in phosphorylation and membrane 
      translocation of NADPH oxidase p47phox subunit in Hcy-treated cells. Addition of 
      folic acid (200 ng/mL) to the culture medium abolished NADPH oxidase-dependent 
      superoxide anion generation in macrophages by preventing phosphorylation of 
      p47phox subunit. Consequently, Hcy-induced NF-kappaB activation and MCP-1 
      expression was inhibited. Such an inhibitory effect of folic acid was independent 
      of its Hcy-lowering ability. Taken together, these results suggest that folic 
      acid treatment can effectively inhibit Hcy-induced oxidative stress and 
      inflammatory responses in macrophages. This may represent one of the mechanisms 
      by which folic acid supplementation exerts a protective effect in cardiovascular 
      disorders.
FAU - Au-Yeung, Kathy K W
AU  - Au-Yeung KK
AD  - Department of Animal Science, University of Manitoba, National Centre for 
      Agri-Food Research in Medicine, Laboratory of Integrative Biology, NCARM, St 
      Boniface Hospital Research Centre, Winnipeg, Canada.
FAU - Yip, Johnny C W
AU  - Yip JC
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 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 11062-77-4 (Superoxides)
RN  - 935E97BOY8 (Folic Acid)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (neutrophil cytosolic factor 1)
SB  - IM
MH  - Cell Line
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Folic Acid/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Homocysteine/pharmacology
MH  - Humans
MH  - Macrophages/*metabolism
MH  - NADPH Oxidases/metabolism
MH  - NF-kappa B/*antagonists & inhibitors/metabolism
MH  - RNA, Messenger/metabolism
MH  - Superoxides/*antagonists & inhibitors/metabolism
EDAT- 2006/07/19 09:00
MHDA- 2006/08/24 09:00
CRDT- 2006/07/19 09:00
PHST- 2006/07/19 09:00 [pubmed]
PHST- 2006/08/24 09:00 [medline]
PHST- 2006/07/19 09:00 [entrez]
AID - 10.1139/Y05-136 [doi]
PST - ppublish
SO  - Can J Physiol Pharmacol. 2006 Jan;84(1):141-7. doi: 10.1139/Y05-136.