Potential involvement of F0F1-ATP(synth)ase and reactive oxygen species in apoptosis induction by the antineoplastic agent erucylphosphohomocholine in glioblastoma cell lines : a mechanism for induction of apoptosis via the 18 kDa mitochondrial translocator protein.
Potential involvement of F0F1-ATP(synth)ase and reactive oxygen species in apoptosis induction by the antineoplastic agent erucylphosphohomocholine in glioblastoma cell lines : a mechanism for induction of apoptosis via the 18 kDa mitochondrial translocator protein.
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DOI：
10.1007/s10495-010-0460-5
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发表时间：
2010-07
期刊：
影响因子：
7.2
通讯作者：
Kugler, Wilfried
中科院分区：
文献类型：
--
作者：
Veenman, Leo;Alten, Julia;Linnemannstons, Karen;Shandalov, Yulia;Zeno, Sivan;Lakomek, Max;Gavish, Moshe;Kugler, Wilfried
关键词：
之前报道了芥子酰磷酸高胆碱（ErPC 3，Erufosine™）在其他高度抗肿瘤的恶性胶质瘤细胞系中诱导细胞凋亡，同时保留它们的非致瘤对应物。我们以前也发现，线粒体18 kDa转运蛋白（TSPO）是所需的ErPC 3诱导凋亡。这些先前的研究也表明活性氧（ROS）的参与。在本研究中，我们进一步研究了ROS产生的潜在参与，线粒体呼吸链的参与，以及线粒体FOF 1-ATP（合成）酶在ErPC 3对U87 MG和U118 MG人胶质母细胞瘤细胞系的促凋亡作用中的作用。为此，细胞用ROS螯合剂丁基羟基茴香醚（BHA），线粒体呼吸链抑制剂鱼藤酮，抗霉素A，myxothiazol和解偶联剂CCCP处理。此外，寡霉素和piceatannol作为线粒体FOF 1-ATP（合成）酶的FO和F1亚基的抑制剂进行了研究。BHA能够减弱ErPC 3诱导的细胞凋亡，包括用心磷脂氧化测定的线粒体ROS生成，以及线粒体膜电位（Δ Km）的崩溃。类似地，我们发现寡霉素减弱了通常由ErPC 3诱导的凋亡和Δ λ m的崩溃，包括伴随的细胞ATP水平的降低。线粒体呼吸链的其他抑制剂，以及piceatannol，没有表现出这样的效果。因此，我们的研究结果有力地指出了线粒体FOF 1-ATP（合成）酶的FO亚基在ErPC 3诱导的凋亡和Δ TSPO的消散以及ErPC 3和TSPO产生的ROS中的作用。
Erucylphosphohomocholine (ErPC3, Erufosine™) was reported previously to induce apoptosis in otherwise highly apoptosis-resistant malignant glioma cell lines while sparing their non-tumorigenic counterparts. We also previously found that the mitochondrial 18 kDa Translocator Protein (TSPO) is required for apoptosis induction by ErPC3. These previous studies also suggested involvement of reactive oxygen species (ROS). In the present study we further investigated the potential involvement of ROS generation, the participation of the mitochondrial respiration chain, and the role of the mitochondrial FOF1-ATP(synth)ase in the pro-apoptotic effects of ErPC3 on U87MG and U118MG human glioblastoma cell lines. For this purpose, cells were treated with the ROS chelator butylated hydroxyanisole (BHA), the mitochondrial respiration chain inhibitors rotenone, antimycin A, myxothiazol, and the uncoupler CCCP. Also oligomycin and piceatannol were studied as inhibitors of the FO and F1 subunits of the mitochondrial FOF1-ATP(synth)ase, respectively. BHA was able to attenuate apoptosis induction by ErPC3, including mitochondrial ROS generation as determined with cardiolipin oxidation, as well as collapse of the mitochondrial membrane potential (Δψm). Similarly, we found that oligomycin attenuated apoptosis and collapse of the Δψm, normally induced by ErPC3, including the accompanying reductions in cellular ATP levels. Other inhibitors of the mitochondrial respiration chain, as well as piceatannol, did not show such effects. Consequently, our findings strongly point to a role for the FO subunit of the mitochondrial FOF1-ATP(synth)ase in ErPC3-induced apoptosis and dissipation of Δψm as well as ROS generation by ErPC3 and TSPO.
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影响因子：
3.5
作者：
Borutaite, V;Morkuniene, R;Brown, GC
通讯作者：
Brown, GC
DOI：
10.1073/pnas.91.13.6103
发表时间：
1994-06-21
影响因子：
11.1
作者：
ISHII, T;LEMAS, MV;TAKEYASU, K
通讯作者：
TAKEYASU, K
影响因子：
2.7
作者：
Cleary, Joanne;Johnson, Kathryn M.;Glick, Gary D.
通讯作者：
Glick, Gary D.
影响因子：
3
作者：
HILGARD, P;KLENNER, T;UNGER, C
通讯作者：
UNGER, C
影响因子：
7.3
作者：
Chen, Wen-Pin;Hung, Li-Man;Su, Ming-Jai
通讯作者：
Su, Ming-Jai