The Effect of Aerobic Respiration Activity on Porphyrin Metabolism in Tumor Cells
The Effect of Aerobic Respiration Activity on Porphyrin Metabolism in Tumor Cells
复制标题
有氧呼吸活动对肿瘤细胞卟啉代谢的影响
DOI：
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
M. Nakajima
中科院分区：
文献类型：
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作者：
Y. Sugiyama;Yuichiro Hagiya;M. Nakajima
bSBI Pharmaceuticals CO., LTD.，Izumi Garden Tower 20F, 1-6-1, Roppongi, Minato-ku, Tokyo, 106-6020, Japan。收稿日期：2012年10月29日，接受日期：2012年12月5日 摘要 我们之前的研究表明，卟啉合成途径中生成血红素的前体5-氨基乙酰丙酸（ALA）通过上调小鼠线粒体呼吸链复合物IV（细胞色素c氧化酶，COX）的蛋白质水平来促进有氧能量代谢。另一方面，肿瘤细胞表现出特有的代谢表型，即 Warburg 效应，即 ATP 生成从氧化磷酸化转变为糖酵解。此外，肿瘤细胞合成血红素的能力有限。因此ALA会诱导肿瘤细胞中卟啉的积累。因此，在本研究中，我们重点关注肿瘤细胞中的能量和卟啉代谢。我们检测了人胃癌细胞系的有氧呼吸活动和卟啉积累水平。测量细胞培养基中COX酶活性和耗氧率。通过荧光测量定量测定与ALA一起孵育的肿瘤细胞中卟啉的积累水平。肿瘤细胞中COX活性低于正常细胞。这些结果表明 COX 活性的降低是 Warburg 效应的关键因素。此外，还观察到细胞系之间 COX 活性、耗氧率和卟啉积累水平的差异。显示高耗氧率的细胞系表现出低卟啉积累。另一方面，显示出低耗氧率的细胞系显示出高卟啉积累。结果，这些数据表明有氧呼吸能力与卟啉积累水平之间存在负相关。
bSBI Pharmaceuticals CO., LTD., Izumi Garden Tower 20F, 1-6-1, Roppongi, Minato-ku, Tokyo,106-6020, Japan. Received 29th October 2012, Accepted 5th December 2012 Summary Our previous research have demonstrated that 5-aminolevulinic acid (ALA), the precursor in the porphyrin synthesis pathway leads to heme, promotes aerobic energy metabolism via up-regulation of protein levels of mitochondrial respiratory chain complex IV (cytochrome c oxidase, COX) in mouse. On the other hand, tumor cells exhibit the characterized metabolic phenotype, the Warburg effect, which is a shift of ATP generation from oxidative phosphorylation to glycolysis. Moreover, tumor cells have a limited capacity of heme synthesis. Therefore ALA induces the accumulation of porphyrin in tumor cells. Hence, in the present study, we focus on energy and porphyrin metabolism in tumor cells. We examined aerobic respiration activities and porphyrin accumulation levels of human gastric cancer cell lines. COX enzyme activity and oxygen consumption rate in the cell culture medium were measured. The porphyrin accumulation level in tumor cells incubated with ALA was quantitatively determined by fluorescence measurement. COX activities in tumor cells were lower than that in normal cells. These results indicates that a reduction of COX activity is critical factor in the Warburg effect. Furthermore, differences in COX activities, oxygen consumption rates and porphyrin accumulation levels were observed among the cell lines. The cell line which showed high oxygen consumption rate exhibited the low porphyrin accumulation. On the other hand, the cell line which showd low oxygen consumption rate exhibited the high porphyrin accumulation. In the result, these data suggest that there is an inverse correlation between aerobic respiration ability and porphyrin accumulation level.
影响因子：
2.9
作者：
BERRY, EA;TRUMPOWER, BL
通讯作者：
TRUMPOWER, BL