The changes of reactive oxygen species and glutathione by MG132, a proteasome inhibitor affect As4.1 juxtaglomerular cell growth and death
The changes of reactive oxygen species and glutathione by MG132, a proteasome inhibitor affect As4.1 juxtaglomerular cell growth and death
复制标题
DOI：
10.1016/j.cbi.2010.01.033
复制
发表时间：
2010-03-30
影响因子：
5.1
通讯作者：
Park, Woo Hyun
中科院分区：
文献类型：
--
作者：
Han, Yong Hwan;Park, Woo Hyun
蛋白酶体抑制剂MG 132已显示通过活性氧（ROS）的形成诱导凋亡性细胞死亡。在这里，我们评估了MG 132对As4.1肾小球细胞的生长和死亡的影响，与ROS和谷胱甘肽（GSH）水平有关。MG 132在48 h时以约0.3-0.4 μ M的IC 50抑制As4.1细胞的生长，并诱导细胞死亡，这伴随着线粒体膜电位（MMP：Delta psi（m））的丧失、Bcl-2的降低、半胱天冬酶-3和-8的活化以及PARP裂解。MG 132增加细胞内ROS水平，包括Of和GSH耗尽的细胞数量。N-乙酰半胱氨酸（NAC，一种众所周知的抗氧化剂）显著降低MG 132处理的As4.1细胞中的ROS水平和GSH耗尽的细胞数量，沿着防止细胞生长抑制、细胞死亡和MMP（Δ psi（m））损失。NAC还降低MG 132的caspase-3活性。L-丁硫酰亚胺亚砜（BSO; GSH合成的抑制剂）或二乙基二硫代氨基甲酸盐（DDC; Cu/Zn-SOD的抑制剂）不影响MG 132处理的As4.1细胞中的细胞生长、死亡、ROS和GSH水平。结论：MG 132通过诱导As4.1细胞凋亡抑制As4.1细胞生长。MG 132引起的ROS和GSH的变化参与了As4.1细胞的生长和死亡。(C)2010爱思唯尔爱尔兰有限公司版权所有。
The proteasome inhibitor MG 132 has been shown to induce apoptotic cell death through the formation of reactive oxygen species (ROS). Here, we evaluated the effects of MG132 on the growth and death of As4.1 juxtaglomerular cells in relation to ROS and glutathione (GSH) levels. MG132 inhibited the growth of As4.1 cells with an IC50 of approximately 0.3-0.4 mu M at 48 h and induced cell death, which was accompanied by the loss of mitochondrial membrane potential (MMP: Delta psi(m)), Bcl-2 decrease, activation of caspase-3 and -8, and PARP cleavage. MG132 increased intracellular ROS levels including Of and GSH depleted cell numbers. N-acetyl cysteine (NAC, a well-known antioxidant) significantly decreased ROS level and GSH depleted cell numbers in MG132-treated As4.1 cells, along with the prevention of cell growth inhibition, cell death and MMP (Delta psi(m)) loss. NAC also decreased the caspase-3 activity of MG132. L-Buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) or diethyldithiocarbamate (DDC; an inhibitor of Cu/Zn-SOD) did not affect cell growth, death, ROS and GSH levels in MG132-treated As4.1 cells. Conclusively, MG132 reduced the growth of As4.1 cells via apoptosis. The changes of ROS and GSH by MG132 were involved in As4.1 cell growth and death. (C) 2010 Elsevier Ireland Ltd. All rights reserved.