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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.


As35 or P35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A. (A) Structures of As35 and P35; (B) Endothelial MT-1A, MT-1E, and MT-2A expression after As35 (upper panels) or P35 (lower panels) treatment. Vascular endothelial cells were treated with or without 10, 20, 50, or 100 µM As35 for 12 h (upper panels) or 5, 10, 20, or 30 µM P35 or 12 h (lower panels). The cells were also treated with 100 µM Sb35, which served as a comparative control. MT-1A, MT-1E, and MT-2A mRNA expression was determined by performing real-time RT-PCR. Data are expressed as the mean ± SE of three representative samples, with each sample obtained from three independent experiments. ** p < 0.01 indicate significantly different from the corresponding control.
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ijms-17-01381-f006: As35 or P35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A. (A) Structures of As35 and P35; (B) Endothelial MT-1A, MT-1E, and MT-2A expression after As35 (upper panels) or P35 (lower panels) treatment. Vascular endothelial cells were treated with or without 10, 20, 50, or 100 µM As35 for 12 h (upper panels) or 5, 10, 20, or 30 µM P35 or 12 h (lower panels). The cells were also treated with 100 µM Sb35, which served as a comparative control. MT-1A, MT-1E, and MT-2A mRNA expression was determined by performing real-time RT-PCR. Data are expressed as the mean ± SE of three representative samples, with each sample obtained from three independent experiments. ** p < 0.01 indicate significantly different from the corresponding control.

Mentions: Understanding the role of the antimony atom in Sb35 molecules in endothelial MT induction is important for understanding the bioactivity of Sb35 as a hybrid molecule. In order to increase the understanding of the role of antimony atom, we next investigated the effects of pnictogen analogues—As35 and P35 (Figure 6A)—on the transcriptional induction of MT-1A, MT-1E, and MT-2A in bovine aortic endothelial cells. As35 significantly increased MT-1A and MT-2A expression similarly to Sb35 (Figure 6B, upper panels). The transcriptional induction of MT-1A and MT-1E by P35 was very weak; however, P35 strongly induced transcription of MT-2A (Figure 6B, lower panels).


Transcriptional Induction of Metallothionein by Tris(pentafluorophenyl)stibane in Cultured Bovine Aortic Endothelial Cells
As35 or P35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A. (A) Structures of As35 and P35; (B) Endothelial MT-1A, MT-1E, and MT-2A expression after As35 (upper panels) or P35 (lower panels) treatment. Vascular endothelial cells were treated with or without 10, 20, 50, or 100 µM As35 for 12 h (upper panels) or 5, 10, 20, or 30 µM P35 or 12 h (lower panels). The cells were also treated with 100 µM Sb35, which served as a comparative control. MT-1A, MT-1E, and MT-2A mRNA expression was determined by performing real-time RT-PCR. Data are expressed as the mean ± SE of three representative samples, with each sample obtained from three independent experiments. ** p < 0.01 indicate significantly different from the corresponding control.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037661&req=5

ijms-17-01381-f006: As35 or P35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A. (A) Structures of As35 and P35; (B) Endothelial MT-1A, MT-1E, and MT-2A expression after As35 (upper panels) or P35 (lower panels) treatment. Vascular endothelial cells were treated with or without 10, 20, 50, or 100 µM As35 for 12 h (upper panels) or 5, 10, 20, or 30 µM P35 or 12 h (lower panels). The cells were also treated with 100 µM Sb35, which served as a comparative control. MT-1A, MT-1E, and MT-2A mRNA expression was determined by performing real-time RT-PCR. Data are expressed as the mean ± SE of three representative samples, with each sample obtained from three independent experiments. ** p < 0.01 indicate significantly different from the corresponding control.
Mentions: Understanding the role of the antimony atom in Sb35 molecules in endothelial MT induction is important for understanding the bioactivity of Sb35 as a hybrid molecule. In order to increase the understanding of the role of antimony atom, we next investigated the effects of pnictogen analogues—As35 and P35 (Figure 6A)—on the transcriptional induction of MT-1A, MT-1E, and MT-2A in bovine aortic endothelial cells. As35 significantly increased MT-1A and MT-2A expression similarly to Sb35 (Figure 6B, upper panels). The transcriptional induction of MT-1A and MT-1E by P35 was very weak; however, P35 strongly induced transcription of MT-2A (Figure 6B, lower panels).

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&ndash;MRE and Nrf2&ndash;ARE pathways, whereas MT-2A expression requires only activation of the MTF-1&ndash;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.