Department of Physiology, Medical School, Chonbuk National University, JeonJu, Republic of Korea.
Anticancer Res. 2009 Nov;29(11):4423-31.
Antimycin A (AMA) inhibits succinate oxidase, NADH oxidase and mitochondrial electron transport chain between cytochrome b and c. Here, we investigated the effects of AMA and/or mitogen-activated protein kinase (MAPK) inhibitors on As4.1 juxtaglomerular cells in relation to cell growth, cell death, reactive oxygen species (ROS) and glutathione (GSH) levels. Treatment with 50 nM AMA inhibited the growth of As4.1 cells at 48 hours and induced apoptosis, which was accompanied by the loss of mitochondrial membrane potential (DeltaPsi(m)). AMA increased ROS levels including that of intracellular O(2)(*-). AMA also induced GSH depletion. MEK inhibitor did not affect cell growth, cell death, DeltaPsi(m) loss, ROS level or GSH depletion in AMA-treated As4.1 cells. c-Jun N-terminal kinase (JNK) inhibitor also did not influence cell growth, cell death, ROS level and GSH depletion but did slightly increase DeltaPsi(m) loss. Treatment with p38 inhibitor magnified cell growth inhibition by AMA and increased cell death, DeltaPsi(m) loss and GSH depletion in AMA-treated As4.1 cells. Conclusively, p38 inhibitor intensified cell death in AMA-treated As4.1 cells. The changes of GSH content rather than ROS level by AMA and/or MAPK inhibitors were more closely related to the growth and death of As4.1 cells.
安密霉素 A（AMA）抑制琥珀酸氧化酶、烟酰胺腺嘌呤二核苷酸氧化酶和细胞色素 b 与 c 之间的线粒体电子传递链。在这里，我们研究了 AMA 和/或丝裂原活化蛋白激酶（MAPK）抑制剂对肾小球旁器细胞（As4.1）的影响，涉及细胞生长、细胞死亡、活性氧（ROS）和谷胱甘肽（GSH）水平。50 nM AMA 处理在 48 小时抑制 As4.1 细胞生长并诱导细胞凋亡，这伴随着线粒体膜电位（DeltaPsi(m)）的丧失。AMA 增加了 ROS 水平，包括细胞内 O(2)(*-)的水平。AMA 还诱导 GSH 耗竭。MEK 抑制剂不影响 AMA 处理的 As4.1 细胞的细胞生长、细胞死亡、DeltaPsi(m)丧失、ROS 水平或 GSH 耗竭。JNK 抑制剂也不影响细胞生长、细胞死亡、ROS 水平和 GSH 耗竭，但轻微增加 DeltaPsi(m)丧失。p38 抑制剂处理放大了 AMA 对细胞生长的抑制作用，并增加了 AMA 处理的 As4.1 细胞的细胞死亡、DeltaPsi(m)丧失和 GSH 耗竭。总之，p38 抑制剂加剧了 AMA 处理的 As4.1 细胞的死亡。GSH 含量的变化而不是 AMA 和/或 MAPK 抑制剂的 ROS 水平与 As4.1 细胞的生长和死亡更为密切相关。
