Microcystin-LR induces apoptosis via NF-κB/iNOS pathway in INS-1 cells.
Microcystin-LR induces apoptosis via NF-κB/iNOS pathway in INS-1 cells.
复制标题
DOI：
10.3390/ijms12074722
复制
发表时间：
2011
影响因子：
5.6
通讯作者：
Wu S
中科院分区：
文献类型：
--
作者：
Ji Y;Lu G;Chen G;Huang B;Zhang X;Shen K;Wu S
蓝藻毒素，尤其是微囊藻毒素，存在于世界各地的富营养化水域中，其对人类和动物健康的潜在影响令人担忧。微囊藻毒素-LR (MC-LR) 是常见的有毒微囊藻毒素同系物之一，经常出现在不同的水系统中。最近的研究表明，细胞凋亡在 MC-LR 诱导的肝细胞毒性作用中起主要作用。然而，MC-LR 在胰腺 β 细胞中的作用尚未完全确定。本研究的目的是评估 MC-LR 对大鼠胰岛素瘤细胞系 INS-1 细胞凋亡的体外可能影响。我们的结果表明，MC-LR 促进 NF-κB 的选择性激活（增加核 p50/p65 易位）并增加诱导一氧化氮合酶 (iNOS) 的 mRNA 和蛋白质水平。 MC-LR 的长期治疗会刺激 iNOS 产生一氧化氮 (NO)，并以剂量依赖性方式诱导 INS-1 细胞凋亡。同时，这种作用被NF-κB抑制剂PDTC抑制，从而逆转了MC-LR诱导的细胞凋亡。我们的观察表明 MC-LR 通过 iNOS 依赖性途径诱导细胞凋亡。众所周知的核转录因子 NF-κB 被激活并介导细胞内一氧化氮合成。我们认为体内慢性 MC-LR 诱导的细胞凋亡可能是 β 细胞功能障碍的原因，是糖尿病发生的关键环境因素。
Cyanobacterial toxins, especially the microcystins, are found in eutrophied waters throughout the world, and their potential to impact on human and animal health is a cause for concern. Microcystin-LR (MC-LR) is one of the common toxic microcystin congeners and occurs frequently in diverse water systems. Recent work suggested that apoptosis plays a major role in the toxic effects induced by MC-LR in hepatocytes. However, the roles of MC-LR in pancreatic beta cells have not been fully established. The aim of the present study was to assess possible in vitro effects of MC-LR on cell apoptosis in the rat insulinoma cell line, INS-1. Our results demonstrated that MC-LR promoted selectively activation of NF-κB (increasing nuclear p50/p65 translocation) and increased the mRNA and protein levels of induced nitric oxide synthase (iNOS). The chronic treatment with MC-LR stimulated nitric oxide (NO) production derived from iNOS and induced apoptosis in a dose dependent manner in INS-1 cells. Meanwhile, this effect was inhibited by the NF-κB inhibitor PDTC, which reversed the apoptosis induced by MC-LR. Our observations indicate that MC-LR induced cell apoptosis via an iNOS-dependent pathway. A well-known nuclear transcription factor, NF-κB, is activated and mediates intracellular nitric oxide synthesis. We suggest that the apoptosis induced by chronic MC-LR in vivo presents a possible cause of β-cell dysfunction, as a key environmental factor in the development of diabetes mellitus.
登录
查看更多内容
影响因子：
7.7
作者：
Darville, MI;Eizirik, DL
通讯作者：
Eizirik, DL
影响因子：
11.2
作者：
Cook, T;Wang, Z;Blumberg, D
通讯作者：
Blumberg, D
影响因子：
--
作者：
CORBETT, JA;KWON, G;MCDANIEL, ML
通讯作者：
MCDANIEL, ML
肝脏 X 受体的激活通过细胞周期停滞抑制胰岛 β 细胞增殖
影响因子：
8.2
作者：
Meng, Z. X.;Nie, J.;Han, X.
通讯作者：
Han, X.
影响因子：
2.8
作者：
Brzuzan, Pawel;Wozny, Maciej;Dobosz, Stefan
通讯作者：
Dobosz, Stefan