Angiogenic potential of 3-nitro-4-hydroxy benzene arsonic acid (roxarsone).
Angiogenic potential of 3-nitro-4-hydroxy benzene arsonic acid (roxarsone).
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DOI：
10.1289/ehp.10885
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发表时间：
2008-04
影响因子：
10.4
通讯作者：
Barchowsky A
中科院分区：
文献类型：
--
作者：
Basu P;Ghosh RN;Grove LE;Klei L;Barchowsky A
洛克萨尔松(3-硝基-4-羟基苯砷酸)是一种砷化合物，广泛用于家禽行业作为饲料添加剂，用于预防球虫病、刺激生长和改善组织色素沉着。关于从鸡粪或鸡肉产品中残留的化合物释放到环境中的洛克沙松对人类健康的潜在影响，人们知之甚少。生长促进和增强的组织色素沉着表明，低水平的洛克沙尔森暴露可能具有类似于无机亚砷酸盐(AsIII)的血管生成潜力。这项研究的目的是在高含量显像管形成试验中使用培养的人主动脉和肺微血管内皮细胞来检验上述假设，并开始发展对这一过程的分子水平的理解。我们使用三维Matrigel实验来探测培养的人内皮细胞中的血管生成，并使用聚合酶链式反应(PCR)阵列来探测洛克沙司酮或AsIII治疗后基因的变化。此外，我们还利用蛋白质印迹分析了蛋白质浓度和活性的变化。研究发现，在较低浓度下，洛克沙尔森的血管生成指数高于AsIII。内皮型一氧化氮合酶(ENOS)活性增加，但对AsIII诱导的血管生成无明显影响。然而，AsIII引起eNOS更迅速和更显著的磷酸化。选择基因的定量PCR阵列显示，这两个化合物对血管生成基因的表达具有不同的、往往相反的作用。结果表明，洛克沙松和AsIII通过明显不同的信号机制促进人内皮细胞血管生成表型。
Roxarsone (3-nitro-4-hydroxy benzene arsonic acid) is an arsenic compound widely used in the poultry industry as a feed additive to prevent coccidiosis, stimulate growth, and to improve tissue pigmentation. Little is known about the potential human health effects from roxarsone released into the environment from chicken waste or from residual compound in chicken products. The growth potentiation and enhanced tissue pigmentation suggest that low levels of roxarsone exposure may have an angiogenic potential similar to that of inorganic arsenite (AsIII). The goal of this investigation was to test the hypothesis described above using cultured human aortic and lung microvascular endothelial cells in high-content imaging tube-forming assays and begin developing a molecular level understanding of the process. We used a three-dimensional Matrigel assay for probing angiogenesis in cultured human endothelial cells, and a polymerase chain reaction (PCR) array to probe the gene changes as a function of roxarsone or AsIII treatment. In addition, we used Western blot analysis for changes in protein concentration and activation. Roxarsone was found to exhibit a higher angiogenic index than AsIII at lower concentrations. Increased endothelial nitric oxide synthase (eNOS) activity was observed for roxarsone but not for AsIII-induced angiogenesis. However, AsIII caused more rapid and pronounced phosphorylation of eNOS. Quantitative PCR array on select genes revealed that the two compounds have different and often opposite effects on angiogenic gene expression. The results demonstrate that roxarsone and AsIII promote angiogenic phenotype in human endothelial cells through distinctly different signaling mechanisms.
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