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The Orphan Nuclear Receptor NR4A1 Protects Pancreatic β-Cells from Endoplasmic Reticulum (ER) Stress-mediated Apoptosis.

Yu C, Cui S, Zong C, Gao W, Xu T, Gao P, Chen J, Qin D, Guan Q, Liu Y, Fu Y, Li X, Wang X - J. Biol. Chem. (2015)

Bottom Line: This conclusion was further confirmed by experiments exploiting siRNA to knockdown NR4A1 expression in MIN6 cells or exploiting NR4A1 knock-out mice.NR4A1 overexpression in MIN6 cells or mouse islets resulted in Survivin up-regulation.In conclusion, NR4A1 protects pancreatic β-cells against ER stress-mediated apoptosis by up-regulating Survivin expression and down-regulating CHOP expression, which we termed as "positive and negative regulation."

View Article: PubMed Central - PubMed

Affiliation: From the The Department of Cell Biology, Shandong University School of Medicine, Jinan, China, 250012.

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Analysis of the effect of TG or PA on NR4A1 expression in MIN6 cells.A and B, relative NR4A1 mRNA levels in response to 0.5 μm TG (A) (DMSO as control) or 0.4 mm PA (B) (BSA as control) at various time points, as determined by qPCR. C and D, protein expression of NR4A1 and CHOP in response to 0.5 μm TG (C) and 0.4 mm PA (D) at various time points, assessed by Western blotting. Densitometric analyses of the blots are shown as curves. The data show the means of three independent experiments, *p < 0.05, ***p < 0.001 versus the DMSO or BSA control.
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Figure 1: Analysis of the effect of TG or PA on NR4A1 expression in MIN6 cells.A and B, relative NR4A1 mRNA levels in response to 0.5 μm TG (A) (DMSO as control) or 0.4 mm PA (B) (BSA as control) at various time points, as determined by qPCR. C and D, protein expression of NR4A1 and CHOP in response to 0.5 μm TG (C) and 0.4 mm PA (D) at various time points, assessed by Western blotting. Densitometric analyses of the blots are shown as curves. The data show the means of three independent experiments, *p < 0.05, ***p < 0.001 versus the DMSO or BSA control.

Mentions: We examined NR4A1 mRNA expression in MIN6 cells treated with TG (0.5 μm) or PA (0.4 mm) over several time points and found that TG treatment induced NR4A1 mRNA expression, which reached its peak at 2 h (Fig. 1A). PA also induced NR4A1 mRNA expression, with a peak at 16 h (Fig. 1B). We also examined NR4A1 protein expression after TG or PA treatment and found that treatment with either TG or PA increased NR4A1 protein expression in MIN6 cells. CHOP is regarded as a marker of TG- or PA-induced ER stress, and we found that both inducers increased CHOP expression (Fig. 1, C and D). These data suggest that inducers of ER stress can induce NR4A1 expression in MIN6 cells.


The Orphan Nuclear Receptor NR4A1 Protects Pancreatic β-Cells from Endoplasmic Reticulum (ER) Stress-mediated Apoptosis.

Yu C, Cui S, Zong C, Gao W, Xu T, Gao P, Chen J, Qin D, Guan Q, Liu Y, Fu Y, Li X, Wang X - J. Biol. Chem. (2015)

Analysis of the effect of TG or PA on NR4A1 expression in MIN6 cells.A and B, relative NR4A1 mRNA levels in response to 0.5 μm TG (A) (DMSO as control) or 0.4 mm PA (B) (BSA as control) at various time points, as determined by qPCR. C and D, protein expression of NR4A1 and CHOP in response to 0.5 μm TG (C) and 0.4 mm PA (D) at various time points, assessed by Western blotting. Densitometric analyses of the blots are shown as curves. The data show the means of three independent experiments, *p < 0.05, ***p < 0.001 versus the DMSO or BSA control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543630&req=5

Figure 1: Analysis of the effect of TG or PA on NR4A1 expression in MIN6 cells.A and B, relative NR4A1 mRNA levels in response to 0.5 μm TG (A) (DMSO as control) or 0.4 mm PA (B) (BSA as control) at various time points, as determined by qPCR. C and D, protein expression of NR4A1 and CHOP in response to 0.5 μm TG (C) and 0.4 mm PA (D) at various time points, assessed by Western blotting. Densitometric analyses of the blots are shown as curves. The data show the means of three independent experiments, *p < 0.05, ***p < 0.001 versus the DMSO or BSA control.
Mentions: We examined NR4A1 mRNA expression in MIN6 cells treated with TG (0.5 μm) or PA (0.4 mm) over several time points and found that TG treatment induced NR4A1 mRNA expression, which reached its peak at 2 h (Fig. 1A). PA also induced NR4A1 mRNA expression, with a peak at 16 h (Fig. 1B). We also examined NR4A1 protein expression after TG or PA treatment and found that treatment with either TG or PA increased NR4A1 protein expression in MIN6 cells. CHOP is regarded as a marker of TG- or PA-induced ER stress, and we found that both inducers increased CHOP expression (Fig. 1, C and D). These data suggest that inducers of ER stress can induce NR4A1 expression in MIN6 cells.

Bottom Line: This conclusion was further confirmed by experiments exploiting siRNA to knockdown NR4A1 expression in MIN6 cells or exploiting NR4A1 knock-out mice.NR4A1 overexpression in MIN6 cells or mouse islets resulted in Survivin up-regulation.In conclusion, NR4A1 protects pancreatic β-cells against ER stress-mediated apoptosis by up-regulating Survivin expression and down-regulating CHOP expression, which we termed as "positive and negative regulation."

View Article: PubMed Central - PubMed

Affiliation: From the The Department of Cell Biology, Shandong University School of Medicine, Jinan, China, 250012.

Show MeSH
Related in: MedlinePlus