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Zinc is essential for the transcription function of Nrf2 in human renal tubule cells in vitro and mouse kidney in vivo under the diabetic condition.

Li B, Cui W, Tan Y, Luo P, Chen Q, Zhang C, Qu W, Miao L, Cai L - J. Cell. Mol. Med. (2014)

Bottom Line: Zn supplement prevented the effects of TPEN and also increased Akt and GSK-3β phosphorylation with a decrease in Nrf2 nuclear exporter, Fyn.All these effects of Zn were abolished by Akt inhibitor.These results suggest the essentiality of Zn for Nrf2 expression and transcription function.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, The Second Hospital of Jilin University, Changchun, China; Kosair Children's Hospital Research Institute, and Departments of Pediatrics and Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA; Department of Nephrology, Jilin Province People's Hospital, Changchun, China.

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Zn is required for Nrf2 expression and function. HK11 cells were treated by Zn at 50 μM for indicated times and then Nrf2 expression was examined by Western blotting assays (A). HK11 cells were treated by HG (G, 27.5 mM) for 48 hrs, Pal (P, 300 μM) for the last 6 hrs and TPEN (T, 8 μM) with or without Zn (50 μM) for the last 30 hrs, and then subject to Western blotting for Nrf2 expression and its downstream gene HO-1 expression (B). Experiments were repeated at least three times and the data are presented as the mean ± SD. a, P < 0.05 versus CN or CM group; b, P < 0.05 versus G/P group; c, P < 0.05 versus G/P/T group. CN: control; CM: hyperosmotic control; G: HG; P: Pal; T: TPEN.
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fig03: Zn is required for Nrf2 expression and function. HK11 cells were treated by Zn at 50 μM for indicated times and then Nrf2 expression was examined by Western blotting assays (A). HK11 cells were treated by HG (G, 27.5 mM) for 48 hrs, Pal (P, 300 μM) for the last 6 hrs and TPEN (T, 8 μM) with or without Zn (50 μM) for the last 30 hrs, and then subject to Western blotting for Nrf2 expression and its downstream gene HO-1 expression (B). Experiments were repeated at least three times and the data are presented as the mean ± SD. a, P < 0.05 versus CN or CM group; b, P < 0.05 versus G/P group; c, P < 0.05 versus G/P/T group. CN: control; CM: hyperosmotic control; G: HG; P: Pal; T: TPEN.

Mentions: To determine the dynamic effect of Zn on Nrf2 expression, HK11 cells were treated with Zn at 50 μM for 3–48 hrs. Nrf2 expression was significantly up-regulated from 6 to 48 hrs (Fig. 3A). To define the effect of Zn levels on the restoration of TPEN-down-regulated Nrf2 expression and function, we administered Zn at 0, 25, 50, 75 and 100 μM for 30 hrs to the cells treated with HG/Pal plus TPEN at 4 μM. Zn induced a dose-dependent expression and nuclear localization of Nrf2, compared to the cells treated with TPEN alone (Figs. S2 and S3), suggesting that Zn is able to restore Nrf2 expression and nuclear translocation that was down-regulated by TPEN.


Zinc is essential for the transcription function of Nrf2 in human renal tubule cells in vitro and mouse kidney in vivo under the diabetic condition.

Li B, Cui W, Tan Y, Luo P, Chen Q, Zhang C, Qu W, Miao L, Cai L - J. Cell. Mol. Med. (2014)

Zn is required for Nrf2 expression and function. HK11 cells were treated by Zn at 50 μM for indicated times and then Nrf2 expression was examined by Western blotting assays (A). HK11 cells were treated by HG (G, 27.5 mM) for 48 hrs, Pal (P, 300 μM) for the last 6 hrs and TPEN (T, 8 μM) with or without Zn (50 μM) for the last 30 hrs, and then subject to Western blotting for Nrf2 expression and its downstream gene HO-1 expression (B). Experiments were repeated at least three times and the data are presented as the mean ± SD. a, P < 0.05 versus CN or CM group; b, P < 0.05 versus G/P group; c, P < 0.05 versus G/P/T group. CN: control; CM: hyperosmotic control; G: HG; P: Pal; T: TPEN.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4119395&req=5

fig03: Zn is required for Nrf2 expression and function. HK11 cells were treated by Zn at 50 μM for indicated times and then Nrf2 expression was examined by Western blotting assays (A). HK11 cells were treated by HG (G, 27.5 mM) for 48 hrs, Pal (P, 300 μM) for the last 6 hrs and TPEN (T, 8 μM) with or without Zn (50 μM) for the last 30 hrs, and then subject to Western blotting for Nrf2 expression and its downstream gene HO-1 expression (B). Experiments were repeated at least three times and the data are presented as the mean ± SD. a, P < 0.05 versus CN or CM group; b, P < 0.05 versus G/P group; c, P < 0.05 versus G/P/T group. CN: control; CM: hyperosmotic control; G: HG; P: Pal; T: TPEN.
Mentions: To determine the dynamic effect of Zn on Nrf2 expression, HK11 cells were treated with Zn at 50 μM for 3–48 hrs. Nrf2 expression was significantly up-regulated from 6 to 48 hrs (Fig. 3A). To define the effect of Zn levels on the restoration of TPEN-down-regulated Nrf2 expression and function, we administered Zn at 0, 25, 50, 75 and 100 μM for 30 hrs to the cells treated with HG/Pal plus TPEN at 4 μM. Zn induced a dose-dependent expression and nuclear localization of Nrf2, compared to the cells treated with TPEN alone (Figs. S2 and S3), suggesting that Zn is able to restore Nrf2 expression and nuclear translocation that was down-regulated by TPEN.

Bottom Line: Zn supplement prevented the effects of TPEN and also increased Akt and GSK-3β phosphorylation with a decrease in Nrf2 nuclear exporter, Fyn.All these effects of Zn were abolished by Akt inhibitor.These results suggest the essentiality of Zn for Nrf2 expression and transcription function.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, The Second Hospital of Jilin University, Changchun, China; Kosair Children's Hospital Research Institute, and Departments of Pediatrics and Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA; Department of Nephrology, Jilin Province People's Hospital, Changchun, China.

Show MeSH
Related in: MedlinePlus