PMID- 12411394
OWN - NLM
STAT- MEDLINE
DCOM- 20021105
LR  - 20190706
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 91
IP  - 9
DP  - 2002 Nov 1
TI  - Rac-dependent monocyte chemoattractant protein-1 production is induced by 
      nutrient deprivation.
PG  - 798-805
AB  - Under ischemic conditions, the vessel wall recruits inflammatory cells. Human 
      aortic endothelial cells (HAECs) exposed to hypoxia followed by reoxygenation 
      produce monocyte chemoattractant protein-1 (MCP-1); however, most experiments 
      have been performed in the presence of nutrient deprivation (ND). We hypothesized 
      that ND rather than hypoxia mediates endothelial MCP-1 production during 
      ischemia, and that the small GTP-binding protein Rac1 and reactive oxygen species 
      (ROS) are involved in this process. ND was generated by shifting HAECs from 10% 
      to 1% FBS. Superoxide production by HAECs was increased 6 to 24 hours after ND, 
      peaking at 18 hours. MCP-1 production was increased over a similar time frame, 
      but peaked later at 24 hours. These effects were blocked by treatment with 
      antioxidants such as superoxide dismutase mimetic and N-acetylcysteine (NAC), or 
      NADPH oxidase inhibitors, DPI and gp91ds-tat. Superoxide and MCP-1 production 
      were enhanced by RacV12 (constitutively active) in the absence of ND, and were 
      inhibited by RacN17 (dominant-negative) adenoviral transduction under ND, 
      suggesting that the small G-protein Rac1 is required. In conclusion, ND, an 
      important component of ischemia, is sufficient to induce MCP-1 production by 
      HAECs, and such production requires a functional Rac1, redox-dependent pathway.
FAU - Lopes, Neuza H M
AU  - Lopes NH
AD  - Division of Cardiology, Department of Medicine, Duke University Medical Center, 
      Durham, NC 27710, USA.
FAU - Vasudevan, Sanjay S
AU  - Vasudevan SS
FAU - Gregg, David
AU  - Gregg D
FAU - Selvakumar, Balakrishnan
AU  - Selvakumar B
FAU - Pagano, Patrick J
AU  - Pagano PJ
FAU - Kovacic, Herve
AU  - Kovacic H
FAU - Goldschmidt-Clermont, Pascal J
AU  - Goldschmidt-Clermont PJ
LA  - eng
GR  - R01 HL-71536/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Antioxidants)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (NF-kappa B)
RN  - 0 (Peptides)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (SN50 peptide)
RN  - 11062-77-4 (Superoxides)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects/physiology
MH  - Antioxidants/pharmacology
MH  - Cell Culture Techniques/methods
MH  - Cell Line
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Culture Media/pharmacology
MH  - Endothelium, Vascular/cytology/drug effects/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Genes, Reporter
MH  - Humans
MH  - NADPH Oxidases/antagonists & inhibitors
MH  - NF-kappa B/antagonists & inhibitors/genetics/metabolism
MH  - Peptides/pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Recombinant Fusion Proteins/antagonists & inhibitors/genetics/metabolism
MH  - Superoxides/metabolism
MH  - Time Factors
MH  - Transfection
MH  - rac1 GTP-Binding Protein/genetics/*metabolism
EDAT- 2002/11/02 04:00
MHDA- 2002/11/26 04:00
CRDT- 2002/11/02 04:00
PHST- 2002/11/02 04:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/11/02 04:00 [entrez]
AID - 10.1161/01.res.0000040421.54108.81 [doi]
PST - ppublish
SO  - Circ Res. 2002 Nov 1;91(9):798-805. doi: 10.1161/01.res.0000040421.54108.81.