Han Yong H, You Bo R, Moon Hwa J, Kim Sung Z, Kim Suhn H, Park Woo H
Department of Physiology, Medical School, Centers for Healthcare Technology Development, Institute for Medical Sciences, Chonbuk National University, JeonJu 561-180, Republic of Korea.
Mol Med Rep. 2010 Jan-Feb;3(1):161-6. doi: 10.3892/mmr_00000234.
Antimycin A (AMA) inhibits succinate oxidase and the mitochondrial electron transport chain between cytochrome b and c. Here, we report on the effects of mitogen-activated protein kinase (MAPK) inhibitors on AMA-treated calf pulmonary artery endothelial cells (CPAEC) in relation to cell death, reactive oxygen species (ROS) and glutathione (GSH). AMA inhibited the growth of CPAEC and also induced cell death, which was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨm). AMA increased ROS levels including O2·-, and depleted GSH cell numbers in CPAEC. All the MAPK (MEK, JNK, p38) inhibitors enhanced cell growth inhibition and death by AMA, and appeared to augment ROS but not O2·- levels in AMA-treated CPAEC. MEK and p38 inhibitors did not increase the number of GSH-depleted cells in AMA-treated CPAEC, but JNK inhibitor significantly did. Each MAPK inhibitor affected cell growth, death, ROS and GSH levels differently in comparison to control CPAEC. In conclusion, the MAPK inhibitors enhanced cell growth inhibition and death by AMA. Changes in ROS and GSH levels by AMA and/or MAPK inhibitors affected growth and death in CPAEC.
抗霉素A（AMA）抑制琥珀酸氧化酶以及细胞色素b和c之间的线粒体电子传递链。在此，我们报告丝裂原活化蛋白激酶（MAPK）抑制剂对AMA处理的小牛肺动脉内皮细胞（CPAEC）在细胞死亡、活性氧（ROS）和谷胱甘肽（GSH）方面的影响。AMA抑制CPAEC的生长并诱导细胞死亡，同时伴有线粒体膜电位（MMP；ΔΨm）的丧失。AMA增加包括超氧阴离子（O2·-）在内的ROS水平，并使CPAEC中的GSH细胞数量减少。所有的MAPK（MEK、JNK、p38）抑制剂均增强了AMA对细胞生长的抑制作用和诱导的细胞死亡，并且似乎增加了AMA处理的CPAEC中的ROS水平，但不增加O2·-水平。MEK和p38抑制剂并未增加AMA处理的CPAEC中GSH耗尽的细胞数量，但JNK抑制剂显著增加了该数量。与对照CPAEC相比，每种MAPK抑制剂对细胞生长、死亡、ROS和GSH水平的影响各不相同。总之，MAPK抑制剂增强了AMA对细胞生长的抑制作用和诱导的细胞死亡。AMA和/或MAPK抑制剂引起的ROS和GSH水平变化影响了CPAEC的生长和死亡。
