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

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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.


The MTF-1–MRE pathway mediates P35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A. (A) Vascular endothelial cells transfected with an MRE reporter vector were treated with or without 1, 5, 10, 20, or 30 µM P35 for 12 h, and MRE-driven transcriptional activity was determined by performing the MRE-directed reporter assay. ** p < 0.01 indicates significantly different from the corresponding control; (B) P35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A after MTF-1 knockdown. Vascular endothelial cells transfected with control or MTF-1 siRNA were treated with or without 10 or 30 µM P35 for 12 h. Data are expressed as the mean ± SE of three representative samples, with each sample obtained from three independent experiments. ** p < 0.01 indicates significantly different from the corresponding siControl.
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ijms-17-01381-f007: The MTF-1–MRE pathway mediates P35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A. (A) Vascular endothelial cells transfected with an MRE reporter vector were treated with or without 1, 5, 10, 20, or 30 µM P35 for 12 h, and MRE-driven transcriptional activity was determined by performing the MRE-directed reporter assay. ** p < 0.01 indicates significantly different from the corresponding control; (B) P35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A after MTF-1 knockdown. Vascular endothelial cells transfected with control or MTF-1 siRNA were treated with or without 10 or 30 µM P35 for 12 h. Data are expressed as the mean ± SE of three representative samples, with each sample obtained from three independent experiments. ** p < 0.01 indicates significantly different from the corresponding siControl.

Mentions: Therefore, we investigated the involvement of the MTF-1–MRE and Nrf2–ARE pathways in the transcriptional induction of MT-2A by P35. P35 significantly increased MRE-driven transcription in a concentration-dependent manner in vascular endothelial cells (Figure 7A). The transcriptional induction of MT-2A by P35 was suppressed in a siRNA-mediated knockdown of MTF-1 (Figure 7B).


Transcriptional Induction of Metallothionein by Tris(pentafluorophenyl)stibane in Cultured Bovine Aortic Endothelial Cells
The MTF-1–MRE pathway mediates P35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A. (A) Vascular endothelial cells transfected with an MRE reporter vector were treated with or without 1, 5, 10, 20, or 30 µM P35 for 12 h, and MRE-driven transcriptional activity was determined by performing the MRE-directed reporter assay. ** p < 0.01 indicates significantly different from the corresponding control; (B) P35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A after MTF-1 knockdown. Vascular endothelial cells transfected with control or MTF-1 siRNA were treated with or without 10 or 30 µM P35 for 12 h. Data are expressed as the mean ± SE of three representative samples, with each sample obtained from three independent experiments. ** p < 0.01 indicates significantly different from the corresponding siControl.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-17-01381-f007: The MTF-1–MRE pathway mediates P35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A. (A) Vascular endothelial cells transfected with an MRE reporter vector were treated with or without 1, 5, 10, 20, or 30 µM P35 for 12 h, and MRE-driven transcriptional activity was determined by performing the MRE-directed reporter assay. ** p < 0.01 indicates significantly different from the corresponding control; (B) P35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A after MTF-1 knockdown. Vascular endothelial cells transfected with control or MTF-1 siRNA were treated with or without 10 or 30 µM P35 for 12 h. Data are expressed as the mean ± SE of three representative samples, with each sample obtained from three independent experiments. ** p < 0.01 indicates significantly different from the corresponding siControl.
Mentions: Therefore, we investigated the involvement of the MTF-1–MRE and Nrf2–ARE pathways in the transcriptional induction of MT-2A by P35. P35 significantly increased MRE-driven transcription in a concentration-dependent manner in vascular endothelial cells (Figure 7A). The transcriptional induction of MT-2A by P35 was suppressed in a siRNA-mediated knockdown of MTF-1 (Figure 7B).

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.