Protective Role of Nuclear Factor E2-Related Factor 2 against Acute Oxidative Stress-Induced Pancreatic β -Cell Damage.
Protective Role of Nuclear Factor E2-Related Factor 2 against Acute Oxidative Stress-Induced Pancreatic β -Cell Damage.
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核因子 E2 相关因子 2 对急性氧化应激诱导的胰腺 β 细胞损伤的保护作用
DOI：
10.1155/2015/639191
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发表时间：
2015
影响因子：
--
通讯作者：
Pi J
中科院分区：
文献类型：
--
作者：
Fu J;Zheng H;Wang H;Yang B;Zhao R;Lu C;Liu Z;Hou Y;Xu Y;Zhang Q;Qu W;Pi J
氧化应激与1型和2型糖尿病中发生的胰腺β细胞功能障碍的发病机制有关。核因子E2相关因子2（NRF 2）是细胞对氧化应激的适应性反应的主要调节因子。本研究发现，具有稳定敲除Nrf 2（Nrf 2-KD）的MIN 6 β细胞和从Nrf 2敲除小鼠分离的胰岛响应于各种应激源表达显著降低水平的抗氧化酶。在杂乱MIN 6细胞或野生型胰岛中，急性暴露于氧化应激物，包括过氧化氢（H2 O2）和S-亚硝基-N-乙酰青霉胺，导致细胞损伤，如通过细胞活力降低、ATP含量降低、胰岛形态变化和/或凋亡生物标志物以浓度和/或时间依赖性方式改变所确定。相反，沉默Nrf 2使MIN 6细胞或胰岛对损伤敏感。此外，用NRF 2激活剂（包括CDDO-Im、富马酸二甲酯（DMF）和叔丁基对苯二酚（tBHQ））预处理MIN 6 β细胞，可保护细胞免受高水平H2 O2诱导的细胞损伤。鉴于活性氧（ROS）参与调节葡萄糖刺激的胰岛素分泌（GSIS），NRF 2的持续激活减弱了葡萄糖触发的ROS信号传导和GSIS，本研究强调了NRF 2可能在糖尿病不同阶段发生的胰腺β细胞功能障碍中发挥的不同作用。
Oxidative stress is implicated in the pathogenesis of pancreatic β-cell dysfunction that occurs in both type 1 and type 2 diabetes. Nuclear factor E2-related factor 2 (NRF2) is a master regulator in the cellular adaptive response to oxidative stress. The present study found that MIN6 β-cells with stable knockdown of Nrf2 (Nrf2-KD) and islets isolated from Nrf2-knockout mice expressed substantially reduced levels of antioxidant enzymes in response to a variety of stressors. In scramble MIN6 cells or wild-type islets, acute exposure to oxidative stressors, including hydrogen peroxide (H2O2) and S-nitroso-N-acetylpenicillamine, resulted in cell damage as determined by decrease in cell viability, reduced ATP content, morphology changes of islets, and/or alterations of apoptotic biomarkers in a concentration- and/or time-dependent manner. In contrast, silencing of Nrf2 sensitized MIN6 cells or islets to the damage. In addition, pretreatment of MIN6 β-cells with NRF2 activators, including CDDO-Im, dimethyl fumarate (DMF), and tert-butylhydroquinone (tBHQ), protected the cells from high levels of H2O2-induced cell damage. Given that reactive oxygen species (ROS) are involved in regulating glucose-stimulated insulin secretion (GSIS) and persistent activation of NRF2 blunts glucose-triggered ROS signaling and GSIS, the present study highlights the distinct roles that NRF2 may play in pancreatic β-cell dysfunction that occurs in different stages of diabetes.
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影响因子：
3.8
作者：
Pi J;Zhang Q;Fu J;Woods CG;Hou Y;Corkey BE;Collins S;Andersen ME
通讯作者：
Andersen ME
影响因子：
7.7
作者：
Pi, Jingbo;Bai, Yushi;Collins, Sheila
通讯作者：
Collins, Sheila
影响因子：
8.2
作者：
Storling, J;Binzer, J;Mandrup-Poulsen, T
通讯作者：
Mandrup-Poulsen, T
DOI：
10.1124/jpet.111.190132
发表时间：
2012-04-01
影响因子：
3.5
作者：
Scannevin, Robert H.;Chollate, Sowmya;Rhodes, Kenneth J.
通讯作者：
Rhodes, Kenneth J.
DOI：
10.1016/j.beem.2012.08.002
发表时间：
2012-12-01
影响因子：
7.4
作者：
Collins, Sheila;Pi, Jingbo;Yehuda-Shnaidman, Einav
通讯作者：
Yehuda-Shnaidman, Einav