Limits...
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.


The Nrf2–ARE pathway mediates Sb35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A. (A) Expression of Nrf2. Vascular endothelial cells transfected with control or Nrf2 siRNA were treated with or without 10, 50, or 100 µM Sb35 for 24 h, and expression of Nrf2 was determined by performing Western blotting; (B) Sb35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A after Nrf2 knockdown. Vascular endothelial cells transfected with control or Nrf2 siRNA were treated with or without 10, 50, 100, 150, or 200 µM Sb35 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

License
getmorefigures.php?uid=PMC5037661&req=5

ijms-17-01381-f005: The Nrf2–ARE pathway mediates Sb35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A. (A) Expression of Nrf2. Vascular endothelial cells transfected with control or Nrf2 siRNA were treated with or without 10, 50, or 100 µM Sb35 for 24 h, and expression of Nrf2 was determined by performing Western blotting; (B) Sb35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A after Nrf2 knockdown. Vascular endothelial cells transfected with control or Nrf2 siRNA were treated with or without 10, 50, 100, 150, or 200 µM Sb35 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: Nrf2 knockdown (Figure 5A) resulted in a markedly lower expression of MT-1A in the presence of Sb35 (Figure 5b, upper panel). In contrast, MT-2A expression in the Nrf2 knockdown and in the presence of Sb35 was unaffected (Figure 5B, lower panel). Sb35 did not induce the transcription of MT-1E (Figure 5b, middle panel). Thus, the transcriptional induction of MT-1A is regulated by both the MTF-1–MRE and Nrf2–ARE pathways whereas that of MT-2A is stimulated by only the MTF-1–MRE pathway in vascular endothelial cells.


Transcriptional Induction of Metallothionein by Tris(pentafluorophenyl)stibane in Cultured Bovine Aortic Endothelial Cells
The Nrf2–ARE pathway mediates Sb35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A. (A) Expression of Nrf2. Vascular endothelial cells transfected with control or Nrf2 siRNA were treated with or without 10, 50, or 100 µM Sb35 for 24 h, and expression of Nrf2 was determined by performing Western blotting; (B) Sb35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A after Nrf2 knockdown. Vascular endothelial cells transfected with control or Nrf2 siRNA were treated with or without 10, 50, 100, 150, or 200 µM Sb35 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

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

ijms-17-01381-f005: The Nrf2–ARE pathway mediates Sb35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A. (A) Expression of Nrf2. Vascular endothelial cells transfected with control or Nrf2 siRNA were treated with or without 10, 50, or 100 µM Sb35 for 24 h, and expression of Nrf2 was determined by performing Western blotting; (B) Sb35-induced transcription of endothelial MT-1A, MT-1E, and MT-2A after Nrf2 knockdown. Vascular endothelial cells transfected with control or Nrf2 siRNA were treated with or without 10, 50, 100, 150, or 200 µM Sb35 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: Nrf2 knockdown (Figure 5A) resulted in a markedly lower expression of MT-1A in the presence of Sb35 (Figure 5b, upper panel). In contrast, MT-2A expression in the Nrf2 knockdown and in the presence of Sb35 was unaffected (Figure 5B, lower panel). Sb35 did not induce the transcription of MT-1E (Figure 5b, middle panel). Thus, the transcriptional induction of MT-1A is regulated by both the MTF-1–MRE and Nrf2–ARE pathways whereas that of MT-2A is stimulated by only the MTF-1–MRE pathway in vascular 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&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.