Department of Physiology, Medical School, Centers for Healthcare Technology Development, Institute for Medical Sciences, Chonbuk National University, JeonJu, Republic of Korea.
Drug Chem Toxicol. 2010 Oct;33(4):367-76. doi: 10.3109/01480540903483458.
MG132, as a proteasome inhibitor, has been shown to induce apoptotic cell death through the formation of reactive oxygen species (ROS). In this study, we investigated the effects of MG132 and/or MAPK inhibitors on As4.1 juxtaglomerular cells in relation to cell growth, cell death, ROS, and glutathione (GSH) levels. MG132 inhibited the growth of As4.1 cells and induced cell death, accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsi(m)) and activation of caspase-3 and -8. MG132 increased ROS levels, and GSH depleted cell numbers. The MEK inhibitor slightly reduced cell growth and caspase-3 activity in MG132-treated As4.1 cells and mildly increased MMP (DeltaPsi(m)) loss and O(2)(-) level. However, it did not increase apoptosis and GSH depletion. The JNK inhibitor did not strongly influence cell growth, cell death, and GSH depletion by MG132, but increased caspase-3 activity, MMP (DeltaPsi(m)) loss, and O(2)(-) level. Treatment with the p38 inhibitor magnified cell-growth inhibition and apoptosis by MG132. This agent also strongly increased caspase-8 activity, MMP (DeltaPsi(m)) loss, O(2)(*-) level, and GSH depletion. Conclusively, the p38 inhibitor strongly intensified cell death in MG132-treated As4.1 cells. The changes of GSH content by MG132 and/or MAPK inhibitors were closely related to the death of As4.1 cells.
MG132 作为一种蛋白酶体抑制剂，已被证明通过形成活性氧物种 (ROS) 诱导细胞凋亡。在这项研究中，我们研究了 MG132 和/或 MAPK 抑制剂对肾小球旁体细胞系 As4.1 的影响，涉及细胞生长、细胞死亡、ROS 和谷胱甘肽 (GSH) 水平。MG132 抑制 As4.1 细胞的生长并诱导细胞死亡，伴随着线粒体膜电位 (MMP; DeltaPsi(m)) 的丧失和 caspase-3 和 -8 的激活。MG132 增加了 ROS 水平，并使 GSH 耗竭细胞数量减少。MEK 抑制剂轻微减少了 MG132 处理的 As4.1 细胞中的细胞生长和 caspase-3 活性，并轻度增加了 MMP (DeltaPsi(m)) 的丧失和 O(2)(-)水平。然而，它并没有增加细胞凋亡和 GSH 耗竭。JNK 抑制剂对 MG132 引起的细胞生长、细胞死亡和 GSH 耗竭没有强烈影响，但增加了 caspase-3 活性、MMP (DeltaPsi(m)) 的丧失和 O(2)(-)水平。用 p38 抑制剂处理放大了 MG132 引起的细胞生长抑制和凋亡。该试剂还强烈增加了 caspase-8 活性、MMP (DeltaPsi(m)) 的丧失、O(2)(*-)水平和 GSH 耗竭。总之，p38 抑制剂强烈加剧了 MG132 处理的 As4.1 细胞中的细胞死亡。MG132 和/或 MAPK 抑制剂对 GSH 含量的影响与 As4.1 细胞的死亡密切相关。
