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首页> 外文期刊>Life sciences >Indole-3-acetic acid increases glutamine utilization by high peroxidase activity-presenting leukocytes.
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Indole-3-acetic acid increases glutamine utilization by high peroxidase activity-presenting leukocytes.

机译：吲哚-3-乙酸通过高过氧化物酶活性代表白细胞提高了谷氨酰胺的利用率。

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摘要

Indole-3-acetic acid (IAA) is toxic for human tumor cells and in association with horseradish peroxidase (HRP) can be used as a new prodrug/enzyme combination for targeted cancer therapy. The toxic effect of IAA on neutrophils, macrophages and lymphocytes is associated with cell peroxidase activity, which is high in neutrophils and low in lymphocytes. The effect of IAA on glucose and glutamine metabolism in leukocytes presenting different peroxidase activities: neutrophils, thioglycollate-elicited macrophages and lymphocytes was investigated. A time-course effect (from 6 to 48 h in culture) of IAA on glucose and glutamine metabolism of neutrophils, thioglycollate-elicited macrophages, and lymphocytes was then carried out. Addition of IAA (0.25 mM) did not have a marked effect on glucose utilization and lactate formation by the three cell types but it raised glutamine consumption and glutamate production by neutrophils and macrophages. IAA had no effect on glutamine consumption and glutamate production by lymphocytes. A strong relationship was found between glutamine utilization (0.999) and glutamate production (0.999) and peroxidase activity. IAA did not change the activities of hexokinase, glucose-6-phosphate dehydrogenase, citrate synthase, lactate dehydrogenase, and phosphate-dependent glutaminase of 24 h cultured neutrophils and lymphocytes. The effect of IAA (1 mM) on glucose and glutamine metabolism was also investigated by 1 h incubated leukocytes in PBS. IAA did not affect glucose and glutamine metabolism of lymphocytes but enhanced glucose and glutamine metabolism by 1 h incubated neutrophils and thioglycollate-elicited macrophages. IAA caused a marked increase on oxygen consumption by neutrophils, which was more pronounced in the presence of the glutamine as compared to glucose. The stimulation of oxygen consumption leads to a reduction in NADH/NAD+ ratio that activates the flux of substrates through the Krebs cycle. Since glutamine is mainly metabolized through the left hand side of the Krebs cycle, a reduction in the redox state of the cells may accelerate the flux of substrates through glutaminolysis. The toxic results presented here show that the affect of IAA in association with peroxidase involves activation of glutamine metabolism.
机译：吲哚-3-乙酸（IAA）对人类肿瘤细胞有毒，与辣根过氧化物酶（HRP）结合可用作靶向癌症治疗的新前药/酶组合。 IAA对中性粒细胞，巨噬细胞和淋巴细胞的毒性作用与细胞过氧化物酶活性有关，后者在中性粒细胞中较高而在淋巴细胞中较低。 IAA对表现出不同过氧化物酶活性的白细胞中葡萄糖和谷氨酰胺代谢的影响：研究了中性粒细胞，巯基乙酸盐诱导的巨噬细胞和淋巴细胞。然后进行了IAA对中性粒细胞，巯基乙酸盐诱导的巨噬细胞和淋巴细胞的葡萄糖和谷氨酰胺代谢的时程效应（培养6至48 h）。加入IAA（0.25 mM）对三种细胞类型的葡萄糖利用和乳酸形成没有明显影响，但会增加嗜中性粒细胞和巨噬细胞的谷氨酰胺消耗和谷氨酸生产。 IAA对淋巴细胞的谷氨酰胺消耗和谷氨酸生产没有影响。发现谷氨酰胺利用率（0.999）与谷氨酸产量（0.999）与过氧化物酶活性之间存在密切关系。 IAA不会改变培养的嗜中性粒细胞和淋巴细胞24小时的己糖激酶，6-磷酸葡萄糖脱氢酶，柠檬酸合酶，乳酸脱氢酶和磷酸盐依赖性谷氨酰胺酶的活性。还通过在PBS中孵育1 h白细胞研究了IAA（1 mM）对葡萄糖和谷氨酰胺代谢的影响。 IAA不会影响淋巴细胞的葡萄糖和谷氨酰胺代谢，但在培养的嗜中性粒细胞和巯基乙酸盐诱导的巨噬细胞中孵育1 h可以增强葡萄糖和谷氨酰胺代谢。 IAA引起中性粒细胞耗氧量的显着增加，与葡萄糖相比，在存在谷氨酰胺的情况下更明显。耗氧量的刺激导致NADH / NAD +比值的降低，从而激活了通过克雷布斯循环的底物通量。由于谷氨酰胺主要通过克雷布斯循环的左侧进行代谢，因此细胞氧化还原态的降低可能会加速谷氨酰胺分解过程中底物的通量。此处显示的毒性结果表明，IAA与过氧化物酶的关系涉及谷氨酰胺代谢的激活。

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