Arsenic promotes angiogenesis in vitro via a heme oxygenase-1-dependent mechanism

Journal Article · Sat May 01 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.01.004· OSTI ID:21344931

Dan, Meng ^[1]; Xin, Wang; Qingshan, Chang; Hitron, Andrew; Zhuo, Zhang ^[2]; Mei, Xu; Gang, Chen; Jia, Luo ^[3]; Binghua, Jiang ^[4]; Jing, Fang ^[1]

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1. Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031 (China)
2. Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States)
3. Department of Internal Medicine, University of Kentucky, Lexington, KY 40536 (United States)
4. Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States)

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 muM) 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.

• OSTI ID: 21344931
• Journal Information: Toxicology and Applied Pharmacology, Vol. 244, Issue 3; Other Information: DOI: 10.1016/j.taap.2010.01.004; PII: S0041-008X(10)00015-3; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANGIOGENESIS
ARSENIC
CARDIOVASCULAR DISEASES
CHROMATIN
CYSTEINE
DNA
ENZYME IMMUNOASSAY
GENES
GROWTH FACTORS
HEME
IN VITRO
LUCIFERASE
MEN
MESSENGER-RNA
MUTAGENESIS
OXYGENASES
PATHOGENESIS
SODIUM
ALKALI METALS
AMINO ACIDS
ANIMALS
BIOASSAY
CARBOXYLIC ACIDS
DISEASES
ELEMENTS
ENZYMES
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
IMMUNOASSAY
MALES
MAMMALS
MAN
METALS
MITOGENS
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXIDASES
OXIDOREDUCTASES
PIGMENTS
PORPHYRINS
PRIMATES
PROTEINS
RNA
SEMIMETALS
THIOLS
VERTEBRATES