PMID- 19622383
OWN - NLM
STAT- MEDLINE
DCOM- 20090923
LR  - 20131121
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 264
IP  - 1-2
DP  - 2009 Oct 1
TI  - Coordinated regulation of angiopoietin-1 and vascular endothelial growth factor 
      by arsenite in human brain microvascular pericytes: implications of 
      arsenite-induced vascular dysfunction.
PG  - 26-31
LID - 10.1016/j.tox.2009.07.008 [doi]
AB  - Arsenite is an environmental toxicant that is associated with vascular disease; 
      however, the underlying mechanism of its toxicity has yet to be elucidated. 
      Vascular stability appears to be tightly regulated by several vasoactive proteins 
      produced by two adjacent vascular cells, endothelial cells (EC) and pericytes. 
      The disruption of vascular stability may be involved in arsenite toxicity. The 
      roles of angipoietins (Ang) and vascular endothelial growth factor (VEGF) in this 
      process have been evaluated, but these studies have mostly been limited to EC. In 
      this study, we used human brain microvascular pericytes (HBMP) to evaluate the 
      effects of arsenite on Ang-1 and VEGF regulation. Ang-2 was reported to be not 
      detected in HBMP. Arsenite decreased Ang-1 secretion in a time and dose-dependent 
      manner, while it increased VEGF secretion. Although arsenite did not alter Ang-1 
      mRNA expression, it increased intracellular Ang-1 protein levels in a 
      dose-dependent manner, suggesting a role for arsenite in the intracellular 
      trapping of Ang-1. Contrary to Ang-1, the expression of VEGF mRNA was 
      dose-dependently up-regulated by arsenite. Treatment with N-actyl-l:-cysteine 
      (NAC) alone decreased the release of Ang-1, but failed to attenuate the 
      arsenite-induced decrease in Ang-1 secretion, while NAC completely blocked the 
      arsenite-stimulated VEGF secretion. These results indicate that reactive oxygen 
      species are involved in the regulation of VEGF, but not of Ang-1, secretion in 
      response to arsenite treatment in pericytes. Furthermore, immunocytochemical 
      analysis using confocal microscopy revealed a colocalization of Ang-1 with actin 
      filaments that occurred independently of tubulin. In conclusion, arsenite 
      decreases Ang-1 secretion and increases VEGF secretion, which may offer new 
      insight into understanding the arsenite toxicity associated with vascular 
      instability and subsequent development of vascular disease.
CI  - 2009 Elsevier Ireland Ltd.
FAU - Park, Jae-Sun
AU  - Park JS
AD  - Center for Biomedical Research, National Institute of Health, Seoul, South Korea.
FAU - Seo, Jungwon
AU  - Seo J
FAU - Kim, Yong-Ou
AU  - Kim YO
FAU - Lee, Ho-Sa
AU  - Lee HS
FAU - Jo, Inho
AU  - Jo I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090719
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Actins)
RN  - 0 (Angiopoietin-1)
RN  - 0 (Arsenites)
RN  - 0 (Teratogens)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - N5509X556J (arsenite)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Actins/biosynthesis/genetics
MH  - Angiopoietin-1/*biosynthesis/genetics
MH  - Arsenites/*toxicity
MH  - Blotting, Western
MH  - Brain Chemistry/*drug effects
MH  - Capillaries/cytology/drug effects/metabolism
MH  - Cells, Cultured
MH  - Cloning, Molecular
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Immunohistochemistry
MH  - Pericytes/*drug effects
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Teratogens/*toxicity
MH  - Vascular Diseases/*chemically induced/metabolism
MH  - Vascular Endothelial Growth Factor A/*biosynthesis/genetics
EDAT- 2009/07/23 09:00
MHDA- 2009/09/24 06:00
CRDT- 2009/07/23 09:00
PHST- 2009/05/19 00:00 [received]
PHST- 2009/07/13 00:00 [revised]
PHST- 2009/07/13 00:00 [accepted]
PHST- 2009/07/23 09:00 [entrez]
PHST- 2009/07/23 09:00 [pubmed]
PHST- 2009/09/24 06:00 [medline]
AID - S0300-483X(09)00365-5 [pii]
AID - 10.1016/j.tox.2009.07.008 [doi]
PST - ppublish
SO  - Toxicology. 2009 Oct 1;264(1-2):26-31. doi: 10.1016/j.tox.2009.07.008. Epub 2009 
      Jul 19.