Journal article
Arsenic promotes angiogenesis in vitro via a heme oxygenase-1-dependent mechanism
Toxicology and applied pharmacology, Vol.244(3), pp.291-299
2010
DOI: 10.1016/j.taap.2010.01.004
PMID: 20083128
Abstract
Angiogenesis and vessel remodeling are fundamental to the pathogenesis of a number of diseases caused by environmental arsenic exposure, including tumorigenesis and cardiovascular diseases. Arsenic (AsIII) has been shown to stimulate angiogenesis and vascular remodeling
in vivo. However, the exact molecular mechanisms accounting for arsenic-induced angiogenesis are not clear. The present study investigates the role of heme oxygenase-1 (HO-1) in sodium arsenite-mediated angiogenesis
in vitro. Transwell assay, three-dimensional Matrigel assay, RT-PCR, ELISA and immunoblotting were used to determine cell migration, vascular tube formation, mRNA and protein expression. Chromatin immunoprecipitation and luciferase assay were applied to examine the DNA binding with protein and HO-1 transcriptional activity. Here, we report that low concentrations of arsenite (0.1–1 μM) stimulated cell migration and vascular tube formation in human microvascular endothelial cells (HMVEC). Arsenite induced HO-1 mRNA and protein expression. Knock down of HO-1 expression decreased arsenite-induced VEGF expression, cell migration, and tube formation. We showed that arsenite promoted dissociation of Bach1 (a transcriptional repressor) from the HO-1 enhancers and increased Nrf2 binding to these elements. Site directed mutagenesis assay identified that Bach1 cysteine residues 557 and 574 were essential for the induction of
HO-1 gene in response to arsenite. These findings demonstrate a role for HO-1 in arsenite-mediated angiogenesis
in vitro.
Details
- Title: Subtitle
- Arsenic promotes angiogenesis in vitro via a heme oxygenase-1-dependent mechanism
- Creators
- Dan Meng - Chinese Academy of SciencesXin Wang - University of KentuckyQingshan Chang - University of KentuckyAndrew Hitron - University of KentuckyZhuo Zhang - University of KentuckyMei Xu - University of KentuckyGang Chen - University of KentuckyJia Luo - University of KentuckyBinghua Jiang - West Virginia UniversityJing Fang - Chinese Academy of SciencesXianglin Shi - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Toxicology and applied pharmacology, Vol.244(3), pp.291-299
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.taap.2010.01.004
- PMID
- 20083128
- ISSN
- 0041-008X
- eISSN
- 1096-0333
- Language
- English
- Date published
- 2010
- Academic Unit
- Pathology; Radiation Oncology
- Record Identifier
- 9984186563302771
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