Department of Physiology, Medical School, Research Institute of Clinical Medicine, Chonbuk National University, JeonJu 561-180, Republic of Korea.
Toxicol In Vitro. 2010 Jun;24(4):1111-8. doi: 10.1016/j.tiv.2010.03.009. Epub 2010 Mar 21.
Antimycin A (AMA) inhibits mitochondrial electron transport chain between cytochrome b and c. Here, we evaluated the effects of AMA on the growth and death of endothelial cells (ECs) in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. AMA inhibited the growth of calf pulmonary artery endothelial cells (CPAEC) and human umbilical vein endothelial cells (HUVEC). AMA also induced apoptosis in both ECs which was accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsi(m)). HUVEC were more sensitive to AMA than CPAEC. AMA increased ROS level in CPAEC but decreased the levels in HUVEC. Z-VAD (pan-caspase inhibitor) mildly prevented apoptosis in AMA-treated ECs without the significant changes of ROS. N-acetyl-cysteine (NAC; a well-known antioxidant) decreased ROS levels in AMA-treated ECs. NAC reduced CPAEC death by AMA but enhanced HUVEC death by it. Furthermore, AMA increased GSH depleted cell numbers in ECs. Buthionine sulfoximine (BSO; an inhibitor of GSH synthesis), showing a pro-apoptotic effect on AMA-treated HUVEC, significantly increased GSH depleted cell number but it did not affect cell death and GSH depletion in AMA-treated CPAEC. In conclusion, AMA inhibited the growth of ECs via caspase-dependent apoptosis. ROS level change by AMA was partially related to CPAEC death, but did not affect HUVEC death. The change of GSH contents by AMA influenced the death of ECs.
安密霉素 A（AMA）抑制细胞色素 b 和 c 之间的线粒体电子传递链。在这里，我们评估了 AMA 对内皮细胞（EC）生长和死亡的影响，以及与活性氧（ROS）和谷胱甘肽（GSH）水平的关系。AMA 抑制小牛肺动脉内皮细胞（CPAEC）和人脐静脉内皮细胞（HUVEC）的生长。AMA 还诱导两种 EC 的凋亡，伴随着线粒体膜电位（MMP；DeltaPsi(m)）的丧失。HUVEC 比 CPAEC 对 AMA 更敏感。AMA 增加了 CPAEC 中的 ROS 水平，但降低了 HUVEC 中的 ROS 水平。Z-VAD（泛半胱天冬酶抑制剂）轻度阻止了 AMA 处理的 EC 中的凋亡，而 ROS 没有明显变化。N-乙酰半胱氨酸（NAC；一种著名的抗氧化剂）降低了 AMA 处理的 EC 中的 ROS 水平。NAC 减少了 AMA 引起的 CPAEC 死亡，但增加了 AMA 引起的 HUVEC 死亡。此外，AMA 增加了 EC 中 GSH 耗竭细胞的数量。丁硫氨酸亚砜（BSO；GSH 合成抑制剂）对 AMA 处理的 HUVEC 表现出促凋亡作用，显著增加了 GSH 耗竭细胞的数量，但它不影响 AMA 处理的 CPAEC 中的细胞死亡和 GSH 耗竭。总之，AMA 通过半胱天冬酶依赖性凋亡抑制 EC 的生长。AMA 引起的 ROS 水平变化部分与 CPAEC 死亡有关，但不影响 HUVEC 死亡。AMA 引起的 GSH 含量变化影响 EC 的死亡。
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