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Transcriptional Induction of Metallothionein by Tris(pentafluorophenyl)stibane in Cultured Bovine Aortic Endothelial Cells

View Article: PubMed Central - PubMed

ABSTRACT

Vascular endothelial cells cover the luminal surface of blood vessels and contribute to the prevention of vascular disorders such as atherosclerosis. Metallothionein (MT) is a low molecular weight, cysteine-rich, metal-binding, inducible protein, which protects cells from the toxicity of heavy metals and active oxygen species. Endothelial MT is not induced by inorganic zinc. Adequate tools are required to investigate the mechanisms underlying endothelial MT induction. In the present study, we found that an organoantimony compound, tris(pentafluorophenyl)stibane, induces gene expression of MT-1A and MT-2A, which are subisoforms of MT in bovine aortic endothelial cells. The data reveal that MT-1A is induced by activation of both the MTF-1–MRE and Nrf2–ARE pathways, whereas MT-2A expression requires only activation of the MTF-1–MRE pathway. The present data suggest that the original role of MT-1 is to protect cells from heavy metal toxicity and oxidative stress in the biological defense system, while that of MT-2 is to regulate intracellular zinc metabolism.

No MeSH data available.


(A) Transcriptional induction of MT-1X in vascular endothelial cells after treatment with organoantimony compounds shown in Table 1. Human brain microvascular endothelial cells were incubated with the organoantimony compounds at 10 µM each for 3 h, and the expression of MT-1X mRNA was determined by real-time RT-PCR; (B) The map of MRE and ARE regions in the bovine MT promoter.
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ijms-17-01381-f001: (A) Transcriptional induction of MT-1X in vascular endothelial cells after treatment with organoantimony compounds shown in Table 1. Human brain microvascular endothelial cells were incubated with the organoantimony compounds at 10 µM each for 3 h, and the expression of MT-1X mRNA was determined by real-time RT-PCR; (B) The map of MRE and ARE regions in the bovine MT promoter.

Mentions: First, we constructed a library of 28 organoantimony compounds (Table 1). We used human vascular endothelial cells in the first experiment to confirm that MT induction by organoantimony compound(s) is possible in human endothelial cells as well as in bovine endothelial cells as described below. We tested the induction of expression of MT-1X—the major MT isoforms in human vascular endothelial cells [30]. As shown in Figure 1A, it was found that Sb35 induces high MT-1X gene expression. As stated below, As35 and P35 as well as Sb35 increased the expression of MT mRNAs, suggesting that the molecular structure of these hybrid molecules is required for the transcriptional induction of endothelial MT. We predict that antimony compounds, which have no ability to induce MT mRNA expression, lack the required molecular structure.


Transcriptional Induction of Metallothionein by Tris(pentafluorophenyl)stibane in Cultured Bovine Aortic Endothelial Cells
(A) Transcriptional induction of MT-1X in vascular endothelial cells after treatment with organoantimony compounds shown in Table 1. Human brain microvascular endothelial cells were incubated with the organoantimony compounds at 10 µM each for 3 h, and the expression of MT-1X mRNA was determined by real-time RT-PCR; (B) The map of MRE and ARE regions in the bovine MT promoter.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037661&req=5

ijms-17-01381-f001: (A) Transcriptional induction of MT-1X in vascular endothelial cells after treatment with organoantimony compounds shown in Table 1. Human brain microvascular endothelial cells were incubated with the organoantimony compounds at 10 µM each for 3 h, and the expression of MT-1X mRNA was determined by real-time RT-PCR; (B) The map of MRE and ARE regions in the bovine MT promoter.
Mentions: First, we constructed a library of 28 organoantimony compounds (Table 1). We used human vascular endothelial cells in the first experiment to confirm that MT induction by organoantimony compound(s) is possible in human endothelial cells as well as in bovine endothelial cells as described below. We tested the induction of expression of MT-1X—the major MT isoforms in human vascular endothelial cells [30]. As shown in Figure 1A, it was found that Sb35 induces high MT-1X gene expression. As stated below, As35 and P35 as well as Sb35 increased the expression of MT mRNAs, suggesting that the molecular structure of these hybrid molecules is required for the transcriptional induction of endothelial MT. We predict that antimony compounds, which have no ability to induce MT mRNA expression, lack the required molecular structure.

View Article: PubMed Central - PubMed

ABSTRACT

Vascular endothelial cells cover the luminal surface of blood vessels and contribute to the prevention of vascular disorders such as atherosclerosis. Metallothionein (MT) is a low molecular weight, cysteine-rich, metal-binding, inducible protein, which protects cells from the toxicity of heavy metals and active oxygen species. Endothelial MT is not induced by inorganic zinc. Adequate tools are required to investigate the mechanisms underlying endothelial MT induction. In the present study, we found that an organoantimony compound, tris(pentafluorophenyl)stibane, induces gene expression of MT-1A and MT-2A, which are subisoforms of MT in bovine aortic endothelial cells. The data reveal that MT-1A is induced by activation of both the MTF-1–MRE and Nrf2–ARE pathways, whereas MT-2A expression requires only activation of the MTF-1–MRE pathway. The present data suggest that the original role of MT-1 is to protect cells from heavy metal toxicity and oxidative stress in the biological defense system, while that of MT-2 is to regulate intracellular zinc metabolism.

No MeSH data available.