Hu Zhenlin, Guo Xueqing, Yu Qi, Qiu Lei, Li Jianzhong, Ying Kang, Guo Cheng, Zhang Junping
Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
FEBS Lett. 2009 Jan 22;583(2):383-8. doi: 10.1016/j.febslet.2008.12.029. Epub 2008 Dec 25.
Adenine nucleotide translocase (ANT) is known as a core component of the mitochondrial permeability transition pore (MPTP) and a key player in cell death. However, its role in camptothecin (CPT)-induced apoptosis has not been examined. We showed that CPT-induced apoptosis in QGY7703 cells and down-regulated the expression of ANT3. Using ANT3 knock-out and overexpression experiments, we provide further evidence that ANT3 plays a contributive role in CPT-induced apoptosis through induction of MPTP. We speculate that the down-regulation of ANT3 upon stimulation with CPT may be part of the molecular basis underlying the mechanism of acquired resistance to CPT.
腺嘌呤核苷酸转位酶(ANT)是线粒体通透性转换孔(MPTP)的核心组成部分,也是细胞死亡的关键参与者。然而,其在喜树碱(CPT)诱导的细胞凋亡中的作用尚未得到研究。我们发现CPT可诱导QGY7703细胞凋亡,并下调ANT3的表达。通过ANT3基因敲除和过表达实验,我们进一步证明ANT3通过诱导MPTP在CPT诱导的细胞凋亡中发挥作用。我们推测,CPT刺激后ANT3的下调可能是CPT获得性耐药机制的分子基础的一部分。