PMID- 12619887
OWN - NLM
STAT- MEDLINE
DCOM- 20031118
LR  - 20190818
IS  - 0300-8177 (Print)
IS  - 0300-8177 (Linking)
VI  - 243
IP  - 1-2
DP  - 2003 Jan
TI  - Homocysteine stimulates inducible nitric oxide synthase expression in 
      macrophages: antagonizing effect of ginkgolides and bilobalide.
PG  - 37-47
AB  - Hyperhomocysteinemia is an independent risk factor for atherosclerotic diseases. 
      Inducible nitric oxide synthase (iNOS) is mainly expressed in macrophages upon 
      stimulation. Overproduction of nitric oxide (NO) by iNOS can exacerbate the 
      development of atherosclerosis. Our previous studies demonstrated that the 
      extract of ginkgo biloba leaves (EGb) inhibited the iNOS-mediated NO production 
      in monocyte-derived macrophage. We also reported that homocysteine could 
      stimulate monocyte chemoattractant protein-1 (MCP-1) expression in vascular cells 
      causing enhanced monocyte chemotaxis. The objective of the present study was to 
      investigate the effect of homocysteine on iNOS-mediated NO production in 
      macrophages and the antagonizing effect of EGb. Human monocytic cell 
      (THP-1)-derived macrophages were incubated with homocysteine for various time 
      periods. Homocysteine at concentrations of 0.05-0.1 mM significantly stimulated 
      NO production and iNOS activity in macrophages via increased expression of iNOS 
      mRNA and protein. The increased iNOS expression was associated with activation of 
      nuclear factor-kappa B (NF-kappaB) arising from reduced expression of inhibitor 
      protein (IkappaB alpha) mRNA as well as increased phosphorylation of IkappaB 
      alpha protein in homocysteine-treated cells. EGb and its terpenoids (ginkgolide 
      A, ginkgolide B and bilobalide) could antagonize the homocysteine effect on iNOS 
      expression in macrophages via their antioxidant effect resulting in attenuation 
      of NF-kappaB activation. Taken together, our results have demonstrated that 
      homocysteine, at pathophysiological concentrations, stimulates iNOS-mediated NO 
      production in macrophages. EGb and its terpenoids can antagonize such stimulatory 
      effect via antioxidation and attenuation of NF-kappaB activation.
FAU - Woo, Connie W H
AU  - Woo CW
AD  - Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong 
      Kong, China.
FAU - Cheung, Filly
AU  - Cheung F
FAU - Chan, Vincent W H
AU  - Chan VW
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  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Antioxidants)
RN  - 0 (Cyclopentanes)
RN  - 0 (Diterpenes)
RN  - 0 (Furans)
RN  - 0 (Ginkgolides)
RN  - 0 (Lactones)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 11062-77-4 (Superoxides)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - DF149B9460 (ginkgolide B)
RN  - EC 1.14.13.39 (NOS2 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - M81D2O8H7U (bilobalide)
RN  - TAZ2DPR77B (ginkgolide A)
SB  - IM
MH  - Antioxidants/pharmacology
MH  - Cell Line
MH  - Cyclopentanes/*pharmacology
MH  - Diterpenes/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Furans/*pharmacology
MH  - Ginkgolides
MH  - Homocysteine/*pharmacology
MH  - Humans
MH  - Lactones/*pharmacology
MH  - Macrophages/*enzymology/metabolism
MH  - Models, Biological
MH  - Monocytes/metabolism
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/antagonists & inhibitors/metabolism
MH  - Nitric Oxide Synthase/antagonists & inhibitors/*biosynthesis
MH  - Nitric Oxide Synthase Type II
MH  - RNA, Messenger/metabolism
MH  - Superoxides/metabolism
MH  - Time Factors
EDAT- 2003/03/07 04:00
MHDA- 2003/12/03 05:00
CRDT- 2003/03/07 04:00
PHST- 2003/03/07 04:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/03/07 04:00 [entrez]
AID - 10.1023/a:1021601512058 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2003 Jan;243(1-2):37-47. doi: 10.1023/a:1021601512058.