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Nr2e1 Deficiency Augments Palmitate-Induced Oxidative Stress in Beta Cells.

Shi X, Deng H, Dai Z, Xu Y, Xiong X, Ma P, Cheng J - Oxid Med Cell Longev (2015)

Bottom Line: At the molecular level, Nr2e1 deficiency augments palmitate-induced oxidative stress.Nr2e1 deficiency also resulted in decreases in antioxidant enzymes and expression level of Nrf2.Together, this study indicated a potential protective effect of Nr2e1 on beta cells, which may serve as a target for the development of novel therapies for diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.

ABSTRACT
Nuclear receptor subfamily 2 group E member 1 (Nr2e1) has been regarded as an essential regulator of the growth of neural stem cells. However, its function elsewhere is unknown. In the present study, we generated Nr2e1 knockdown MIN6 cells and studied whether Nr2e1 knockdown affected basal beta cell functions such as proliferation, cell death, and insulin secretion. We showed that knockdown of Nr2e1 in MIN6 cells resulted in increased sensitivity to lipotoxicity, decreased proliferation, a partial G0/G1 cell-cycle arrest, and higher rates of apoptosis. Moreover, Nr2e1 deficiency exaggerates palmitate-induced impairment in insulin secretion. At the molecular level, Nr2e1 deficiency augments palmitate-induced oxidative stress. Nr2e1 deficiency also resulted in decreases in antioxidant enzymes and expression level of Nrf2. Together, this study indicated a potential protective effect of Nr2e1 on beta cells, which may serve as a target for the development of novel therapies for diabetes.

No MeSH data available.


Related in: MedlinePlus

Nr2e1 silencing suppressed proliferation of MIN6 cells. (a) Comparison of cell-cycle distribution between control (MIN6-shc) and Nr2e1 silenced (MIN6-sh2 and MIN6-sh3) cells. (b) Percentage of EdU+ MIN6 cells cultured with EdU for 4 h. (c) Representative images (20x magnification) of MIN6 cells labeled with EdU. Data represent means ± SD of three observations; ∗P ≤ 0.05; ∗∗P ≤ 0.01 (comparing silenced versus MIN6-shc cells).
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fig3: Nr2e1 silencing suppressed proliferation of MIN6 cells. (a) Comparison of cell-cycle distribution between control (MIN6-shc) and Nr2e1 silenced (MIN6-sh2 and MIN6-sh3) cells. (b) Percentage of EdU+ MIN6 cells cultured with EdU for 4 h. (c) Representative images (20x magnification) of MIN6 cells labeled with EdU. Data represent means ± SD of three observations; ∗P ≤ 0.05; ∗∗P ≤ 0.01 (comparing silenced versus MIN6-shc cells).

Mentions: To determine if the decreased beta cell viability resulted from changes to beta cell proliferation, we investigated MIN6 cell proliferation rates by EdU incorporation assay. Labeling of cells with EdU and Hochest 33342 showed that, compared with the MIN6-shc cells, the knockdown of Nr2e1 decreased the percentage of EdU-positive cells (Figures 3(b) and 3(c)). The result suggests that Nr2e1 silencing could inhibit MIN6 cell proliferation. We then checked if the knockdown of Nr2e1 altered MIN6 cells cell-cycle distribution. The result showed that, compared to MIN6-shc cells, MIN6-sh2 cells and MIN6-sh3 cells had an increased percentage of G0/G1-phase cells and decreased percentage of S-phase cells (Figure 3(a)). These results indicate that MIN6-sh2 and MIN6-sh3 cells proliferate at a lower rate due to a partial inhibition of the G0/G1 phase of the cell cycle.


Nr2e1 Deficiency Augments Palmitate-Induced Oxidative Stress in Beta Cells.

Shi X, Deng H, Dai Z, Xu Y, Xiong X, Ma P, Cheng J - Oxid Med Cell Longev (2015)

Nr2e1 silencing suppressed proliferation of MIN6 cells. (a) Comparison of cell-cycle distribution between control (MIN6-shc) and Nr2e1 silenced (MIN6-sh2 and MIN6-sh3) cells. (b) Percentage of EdU+ MIN6 cells cultured with EdU for 4 h. (c) Representative images (20x magnification) of MIN6 cells labeled with EdU. Data represent means ± SD of three observations; ∗P ≤ 0.05; ∗∗P ≤ 0.01 (comparing silenced versus MIN6-shc cells).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4663339&req=5

fig3: Nr2e1 silencing suppressed proliferation of MIN6 cells. (a) Comparison of cell-cycle distribution between control (MIN6-shc) and Nr2e1 silenced (MIN6-sh2 and MIN6-sh3) cells. (b) Percentage of EdU+ MIN6 cells cultured with EdU for 4 h. (c) Representative images (20x magnification) of MIN6 cells labeled with EdU. Data represent means ± SD of three observations; ∗P ≤ 0.05; ∗∗P ≤ 0.01 (comparing silenced versus MIN6-shc cells).
Mentions: To determine if the decreased beta cell viability resulted from changes to beta cell proliferation, we investigated MIN6 cell proliferation rates by EdU incorporation assay. Labeling of cells with EdU and Hochest 33342 showed that, compared with the MIN6-shc cells, the knockdown of Nr2e1 decreased the percentage of EdU-positive cells (Figures 3(b) and 3(c)). The result suggests that Nr2e1 silencing could inhibit MIN6 cell proliferation. We then checked if the knockdown of Nr2e1 altered MIN6 cells cell-cycle distribution. The result showed that, compared to MIN6-shc cells, MIN6-sh2 cells and MIN6-sh3 cells had an increased percentage of G0/G1-phase cells and decreased percentage of S-phase cells (Figure 3(a)). These results indicate that MIN6-sh2 and MIN6-sh3 cells proliferate at a lower rate due to a partial inhibition of the G0/G1 phase of the cell cycle.

Bottom Line: At the molecular level, Nr2e1 deficiency augments palmitate-induced oxidative stress.Nr2e1 deficiency also resulted in decreases in antioxidant enzymes and expression level of Nrf2.Together, this study indicated a potential protective effect of Nr2e1 on beta cells, which may serve as a target for the development of novel therapies for diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.

ABSTRACT
Nuclear receptor subfamily 2 group E member 1 (Nr2e1) has been regarded as an essential regulator of the growth of neural stem cells. However, its function elsewhere is unknown. In the present study, we generated Nr2e1 knockdown MIN6 cells and studied whether Nr2e1 knockdown affected basal beta cell functions such as proliferation, cell death, and insulin secretion. We showed that knockdown of Nr2e1 in MIN6 cells resulted in increased sensitivity to lipotoxicity, decreased proliferation, a partial G0/G1 cell-cycle arrest, and higher rates of apoptosis. Moreover, Nr2e1 deficiency exaggerates palmitate-induced impairment in insulin secretion. At the molecular level, Nr2e1 deficiency augments palmitate-induced oxidative stress. Nr2e1 deficiency also resulted in decreases in antioxidant enzymes and expression level of Nrf2. Together, this study indicated a potential protective effect of Nr2e1 on beta cells, which may serve as a target for the development of novel therapies for diabetes.

No MeSH data available.


Related in: MedlinePlus