PMID- 16257644
OWN - NLM
STAT- MEDLINE
DCOM- 20060420
LR  - 20071114
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 39
IP  - 10
DP  - 2005 Nov 15
TI  - Peroxynitrite increases VEGF expression in vascular endothelial cells via STAT3.
PG  - 1353-61
AB  - Increased expression of vascular endothelial growth factor (VEGF) has been 
      correlated with increased oxidative stress and formation of peroxynitrite in 
      numerous disease conditions, including diabetic microangiopathy, tumor 
      angiogenesis, and atherosclerosis. In this study we tested the hypothesis that 
      peroxynitrite stimulates VEGF expression. Treatment of microvascular endothelial 
      cells with exogenous peroxynitrite induced a time- and dose-dependent increase in 
      VEGF mRNA, which peaked within 1 h of treatment at a concentration of 100 muM. 
      The increase in VEGF mRNA was followed by a significant increase in VEGF protein. 
      To define the molecular mechanisms involved, the effect of peroxynitrite was 
      determined on the activation of two transcription factors known to regulate VEGF 
      expression during hypoxia and tumor angiogenesis-signal transducer and activator 
      of transcription 3 (STAT3) and hypoxia-inducible factor-1 (HIF-1). Peroxynitrite 
      caused activation and nuclear translocation of STAT3, but not HIF-1. Moreover, 
      transduction of endothelial cells with dominant-negative STAT3 abrogated the 
      peroxynitrite-induced increase in VEGF mRNA. The increase in VEGF mRNA was also 
      blocked by inhibitors of transcription and was unaffected by the inhibition of 
      protein synthesis. These results indicate that peroxynitrite causes increased 
      expression of VEGF in vascular endothelial cells by a process that requires the 
      activation of STAT3.
FAU - Platt, Daniel H
AU  - Platt DH
AD  - Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA.
FAU - Bartoli, Manuela
AU  - Bartoli M
FAU - El-Remessy, Azza B
AU  - El-Remessy AB
FAU - Al-Shabrawey, Mohamed
AU  - Al-Shabrawey M
FAU - Lemtalsi, Tahira
AU  - Lemtalsi T
FAU - Fulton, David
AU  - Fulton D
FAU - Caldwell, Ruth B
AU  - Caldwell RB
LA  - eng
GR  - R01-NEI-04618/PHS HHS/United States
GR  - R01-NEI-11766/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Free Radicals)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (RNA, Messenger)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Blotting, Western
MH  - Cattle
MH  - Cell Movement
MH  - Cell Nucleus/metabolism
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/*cytology/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Free Radicals
MH  - Gene Expression Regulation
MH  - Genes, Dominant
MH  - Genetic Vectors
MH  - Green Fluorescent Proteins/metabolism
MH  - Hypoxia-Inducible Factor 1/metabolism
MH  - Immunoblotting
MH  - Microcirculation
MH  - Microscopy, Fluorescence
MH  - Muscle, Smooth/cytology
MH  - Oxidative Stress
MH  - Peroxynitrous Acid/chemistry/metabolism/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - STAT3 Transcription Factor/*metabolism
MH  - Time Factors
MH  - Transcription, Genetic
MH  - Vascular Endothelial Growth Factor A/*biosynthesis/genetics/metabolism
EDAT- 2005/11/01 09:00
MHDA- 2006/04/21 09:00
CRDT- 2005/11/01 09:00
PHST- 2005/02/25 00:00 [received]
PHST- 2005/06/20 00:00 [revised]
PHST- 2005/06/25 00:00 [accepted]
PHST- 2005/11/01 09:00 [pubmed]
PHST- 2006/04/21 09:00 [medline]
PHST- 2005/11/01 09:00 [entrez]
AID - S0891-5849(05)00364-3 [pii]
AID - 10.1016/j.freeradbiomed.2005.06.015 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2005 Nov 15;39(10):1353-61. doi: 
      10.1016/j.freeradbiomed.2005.06.015.