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

Dan Meng; Xin Wang; Qingshan Chang; Andrew Hitron; Zhuo Zhang; Mei Xu; Gang Chen; Jia Luo; Binghua Jiang; Jing Fang; Xianglin Shi

doi:10.1016/j.taap.2010.01.004

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

Dan Meng, Xin Wang, Qingshan Chang, Andrew Hitron, Zhuo Zhang, Mei Xu, Gang Chen, Jia Luo, Binghua Jiang, Jing Fang, Xianglin Shi

Research output: Contribution to journal › Article › peer-review

71 Scopus citations

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.

Original language	English
Pages (from-to)	291-299
Number of pages	9
Journal	Toxicology and Applied Pharmacology
Volume	244
Issue number	3
DOIs	https://doi.org/10.1016/j.taap.2010.01.004
State	Published - May 2010

Bibliographical note

Funding Information:
We gratefully acknowledge the technical assistance of Hong Lin. This research was supported by National Institutes of Health Grants R01CA119028-01 , R01CA116697-01A2, R01ES015375-01 , and R01ES015518-01A1 . Dan Meng was supported by National Natural Science Foundation of China ( No.30600245 ). The authors gratefully acknowledge the support of K.C.Wong Education Foundation, Hong Kong, China.

Keywords

Angiogenesis
Arsenic
Bach1
Endothelial
Heme oxygenase 1
Nrf2

ASJC Scopus subject areas

Toxicology
Pharmacology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.taap.2010.01.004

Cite this

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title = "Arsenic promotes angiogenesis in vitro via a heme oxygenase-1-dependent mechanism",

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.",

keywords = "Angiogenesis, Arsenic, Bach1, Endothelial, Heme oxygenase 1, Nrf2",

author = "Dan Meng and Xin Wang and Qingshan Chang and Andrew Hitron and Zhuo Zhang and Mei Xu and Gang Chen and Jia Luo and Binghua Jiang and Jing Fang and Xianglin Shi",

note = "Funding Information: We gratefully acknowledge the technical assistance of Hong Lin. This research was supported by National Institutes of Health Grants R01CA119028-01 , R01CA116697-01A2, R01ES015375-01 , and R01ES015518-01A1 . Dan Meng was supported by National Natural Science Foundation of China ( No.30600245 ). The authors gratefully acknowledge the support of K.C.Wong Education Foundation, Hong Kong, China.",

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AU - Chang, Qingshan

AU - Hitron, Andrew

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AU - Xu, Mei

AU - Chen, Gang

AU - Luo, Jia

AU - Jiang, Binghua

AU - Fang, Jing

AU - Shi, Xianglin

N1 - Funding Information: We gratefully acknowledge the technical assistance of Hong Lin. This research was supported by National Institutes of Health Grants R01CA119028-01 , R01CA116697-01A2, R01ES015375-01 , and R01ES015518-01A1 . Dan Meng was supported by National Natural Science Foundation of China ( No.30600245 ). The authors gratefully acknowledge the support of K.C.Wong Education Foundation, Hong Kong, China.

PY - 2010/5

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N2 - 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.

AB - 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.

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KW - Bach1

KW - Endothelial

KW - Heme oxygenase 1

KW - Nrf2

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SN - 0041-008X

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SP - 291

EP - 299

JO - Toxicology and Applied Pharmacology

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ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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