IMPAIRED MITOCHONDRIAL RESPIRATION AND STIMULATED GLYCOLYSIS BY M-IODOBENZYLGUANIDINE (METAIODOBENZYLGUANIDINE)
IMPAIRED MITOCHONDRIAL RESPIRATION AND STIMULATED GLYCOLYSIS BY M-IODOBENZYLGUANIDINE (METAIODOBENZYLGUANIDINE)
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DOI：
10.1002/ijc.2910460223
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发表时间：
1990-08-15
影响因子：
6.4
通讯作者：
SMETS, LA
中科院分区：
文献类型：
--
作者：
LOESBERG, C;VANROOIJ, H;SMETS, LA
间碘苯甲基胍(MIBG)是一种神经递质去甲肾上腺素的功能类似物。放射性~(131)I-MIBG作为肿瘤靶向的放射性药物在肾上腺素能肿瘤的诊断和治疗中得到了广泛的应用。此前已证明，天然MIBG在培养细胞中具有细胞毒性，并在使用无毒方案时在动物身上产生抗肿瘤反应。本研究观察了MIBG对大鼠肝线粒体和多种肿瘤细胞系(人神经母细胞瘤SK-N-SH、小鼠神经母细胞瘤N1E115和小鼠淋巴肉瘤S49)的作用。结果表明，MIBG可抑制肝脏线粒体呼吸链复合体I的呼吸，但不影响F1-ATP酶。在细胞系中，线粒体呼吸的损害是明显的，表现为氧耗减少和细胞内ATP水平降低。作为对这一效应的反应，糖酵解通量被刺激，表现为葡萄糖消耗和乳酸产生的增加。MIBG的细胞毒性与药物引起的糖代谢改变成正比。
m-Iodobenzylguanidine (MIBG) is a functional analogue of the neurotransmitter norepinephrine. Radio-iodinated 131I-MIBG is used clinically as a tumor-targeted radiopharmaceutical agent in the diagnosis and treatment of adrenergic tumors. Native MIBG has previously been demonstrated to be cytotoxic in cultured cells and to produce anti-tumor responses in animals when non-toxic schedules are used. In this study the effect of MIBG was investigated on isolated rat liver mitochondria and on various tumor cell lines (human neuroblastoma SK-N-SH, mouse neuroblastoma N1E115 and mouse lymphosarcoma S49). Results revealed that MIBG inhibits respiration of isolated liver mitochondria at complex I of the respiratory chain, without affect F1 ATP-ase. In cell lines, impairment of the mitochondrial respiration was evident from reduced oxygen consumption and decreased intracellular ATP levels. In response to this effect, the glycolytic flux was stimulated as shown by increased glucose consumption and lactic acid production. Cytotoxicity of MIBG was proportional to drug-induced alterations in glucose metabolism.