PMID- 12006387
OWN - NLM
STAT- MEDLINE
DCOM- 20020619
LR  - 20190901
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 22
IP  - 5
DP  - 2002 May 1
TI  - Role of isoprenylcysteine carboxyl methyltransferase in tumor necrosis 
      factor-alpha stimulation of expression of vascular cell adhesion molecule-1 in 
      endothelial cells.
PG  - 759-64
AB  - We have previously shown that cytokine stimulation of the expression of vascular 
      cell adhesion molecule-1 (VCAM-1), but not that of intercellular adhesion 
      molecule-1 (ICAM-1), is redox sensitive in endothelial cells. Here, we 
      investigated the role of isoprenylcysteine carboxyl methyltransferase (ICMTase), 
      which methylates isoprenylated CAAX (where C indicates cysteine; A, aliphatic 
      amino acids; and X, almost any other amino acid) proteins, including Rac1, a 
      component of superoxide-generating NAD(P)H oxidase, in the expression of VCAM-1. 
      Pretreatment of endothelial cells with N-acetyl-S-farnesyl-L-cysteine (AFC) or 
      N-acetyl-S-geranylgeranyl-L-cysteine (AGGC), specific inhibitors of ICMTase, 
      inhibited the tumor necrosis factor-alpha (TNF-alpha) stimulation of mRNA 
      expression of VCAM-1 but not that of ICAM-1. Endothelial cells expressed 
      constitutively active ICMTase, as suggested by the presence of methylated Rac1 
      and the methylation of AFC by the cells. TNF-alpha stimulation of the cells 
      significantly increased the methylation of AFC and Rac1 in endothelial cells. 
      That ICMTase was a component of the redox-sensitive signaling pathway was also 
      suggested by the AFC inhibition of the generation of reactive oxygen species by 
      TNF-alpha. Interestingly, the dominant-negative isoform of Rac1 was not selective 
      but inhibited the TNF-alpha stimulation of the mRNA expression of VCAM-1 and 
      ICAM-1. Thus, ICMTase is a critical component of the redox-sensitive 
      VCAM-1-selective signaling pathway, and it appears to activate a discrete 
      inflammatory signaling pathway, at least in part, through the methylation of 
      Rac1.
FAU - Ahmad, Mushtaq
AU  - Ahmad M
AD  - Division of Cardiology, Department of Medicine, Emory University School of 
      Medicine, Atlanta, Ga 30322, USA. mahmad@emory.edu
FAU - Zhang, Yan
AU  - Zhang Y
FAU - Zhang, Yong
AU  - Zhang Y
FAU - Papharalambus, Christopher
AU  - Papharalambus C
FAU - Alexander, R Wayne
AU  - Alexander RW
LA  - eng
GR  - HL-60728-04/HL/NHLBI NIH HHS/United States
GR  - HL-66508-01/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Antigens, Polyomavirus Transforming)
RN  - 0 (Diterpenes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (N-acetyl-S-geranylgeranyl-cysteine)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.1.1.- (Protein Methyltransferases)
RN  - EC 2.1.1.100 (protein-S-isoprenylcysteine O-methyltransferase)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
RN  - K848JZ4886 (Cysteine)
RN  - KK6984C8O3 (N-acetyl-S-farnesylcysteine)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/adverse effects/*analogs & derivatives/metabolism/pharmacology
MH  - Antigens, Polyomavirus Transforming
MH  - Aorta/cytology/virology
MH  - Cell Line, Transformed/virology
MH  - Cell Survival/drug effects
MH  - Cysteine/adverse effects/*analogs & derivatives/pharmacology
MH  - Diterpenes/adverse effects/pharmacology
MH  - Endothelium, Vascular/cytology/drug effects/*enzymology/virology
MH  - Enzyme Inhibitors/adverse effects/metabolism/pharmacology
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Intercellular Adhesion Molecule-1/biosynthesis
MH  - Methylation
MH  - Protein Methyltransferases/metabolism/*physiology
MH  - Tumor Necrosis Factor-alpha/*physiology
MH  - Vascular Cell Adhesion Molecule-1/biosynthesis/*physiology
MH  - rac1 GTP-Binding Protein/metabolism
EDAT- 2002/05/15 10:00
MHDA- 2002/06/20 10:01
CRDT- 2002/05/15 10:00
PHST- 2002/05/15 10:00 [pubmed]
PHST- 2002/06/20 10:01 [medline]
PHST- 2002/05/15 10:00 [entrez]
AID - 10.1161/01.atv.0000015884.61894.dc [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2002 May 1;22(5):759-64. doi: 
      10.1161/01.atv.0000015884.61894.dc.