Department of Internal Medicine, University of Perugia, Via del Giochetto, 06122 Perugia, Italy.
J Bioenerg Biomembr. 2011 Oct;43(5):507-18. doi: 10.1007/s10863-011-9375-2. Epub 2011 Jul 21.
Most cancer cells, including GL15 glioblastoma cells, rely on glycolysis for energy supply. The effect of antiglycolytic bromopyruvate on respiratory parameters and viability of GL15 cells was investigated. Bromopyruvate caused Δψ(m) and MTT collapse, ATP decrease, and cell viability loss without involving apoptotic or necrotic pathways. The autophagy marker LC3-II was increased. Δψ(m) decrease was accompanied by reactive oxygen species (ROS) increase and cytochrome c (cyt c) disappearance, suggesting a link between free radical generation and intramitochondrial cyt c degradation. Indeed, the free radical inducer menadione caused a decrease in cyt c that was reversed by N-acetylcysteine. Cyt c is tightly bound to the inner mitochondrial membrane in GL15 cells, which may confer protein peroxidase activity, resulting in auto-oxidation and protein targeting to degradation in the presence of ROS. This process is directed towards impairment of the apoptotic cyt c cascade, although cells are committed to die.
大多数癌细胞，包括 GL15 神经胶质瘤细胞，都依赖糖酵解来提供能量。本研究旨在探讨抗糖酵解溴丙酮酸对 GL15 细胞呼吸参数和活力的影响。溴丙酮酸导致 Δψ(m) 和 MTT 崩溃、ATP 减少和细胞活力丧失，而不涉及凋亡或坏死途径。自噬标志物 LC3-II 增加。Δψ(m) 的减少伴随着活性氧 (ROS) 的增加和细胞色素 c (cyt c) 的消失，表明自由基的产生与线粒体内部 cyt c 的降解之间存在联系。事实上，自由基诱导剂甲萘醌引起 cyt c 的减少，而 N-乙酰半胱氨酸可以逆转这种减少。在 GL15 细胞中，cyt c 与线粒体内膜紧密结合，这可能赋予其蛋白过氧化物酶活性，导致在 ROS 存在的情况下发生自身氧化和蛋白靶向降解。尽管细胞已经决定死亡，但这个过程旨在损害凋亡 cyt c 级联。
