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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

Effect of Nr2e1 on Nrf2 expression levels. (a) Relative expression level of Nfe2l2 mRNA in MIN6-shc, MIN6-sh2, and MIN6-sh3 cells. (b) Nrf2 protein levels. Results are means ± SD. ∗P < 0.05 compared to MIN6-shc.
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fig7: Effect of Nr2e1 on Nrf2 expression levels. (a) Relative expression level of Nfe2l2 mRNA in MIN6-shc, MIN6-sh2, and MIN6-sh3 cells. (b) Nrf2 protein levels. Results are means ± SD. ∗P < 0.05 compared to MIN6-shc.

Mentions: Because of the decreases observed in antioxidant enzymes levels, we hypothesized that Nr2e1 may modify key regulators of antioxidant genes. The Nrf2 transcription factor is an important activator of antioxidant genes. We next examined levels of Nrf2 protein and its corresponding mRNA (Nfe2l2). As shown in Figure 7, compared with control cells, knockdown of Nr2e1 resulted in a reduction in Nfe2l2 mRNA level. Immunoblots of MIN6 cells showed that Nrf2 protein levels paralleled the observed transcript levels.


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)

Effect of Nr2e1 on Nrf2 expression levels. (a) Relative expression level of Nfe2l2 mRNA in MIN6-shc, MIN6-sh2, and MIN6-sh3 cells. (b) Nrf2 protein levels. Results are means ± SD. ∗P < 0.05 compared to MIN6-shc.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig7: Effect of Nr2e1 on Nrf2 expression levels. (a) Relative expression level of Nfe2l2 mRNA in MIN6-shc, MIN6-sh2, and MIN6-sh3 cells. (b) Nrf2 protein levels. Results are means ± SD. ∗P < 0.05 compared to MIN6-shc.
Mentions: Because of the decreases observed in antioxidant enzymes levels, we hypothesized that Nr2e1 may modify key regulators of antioxidant genes. The Nrf2 transcription factor is an important activator of antioxidant genes. We next examined levels of Nrf2 protein and its corresponding mRNA (Nfe2l2). As shown in Figure 7, compared with control cells, knockdown of Nr2e1 resulted in a reduction in Nfe2l2 mRNA level. Immunoblots of MIN6 cells showed that Nrf2 protein levels paralleled the observed transcript levels.

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