Minchenko D O, Kundieva A V, Tsuchihara K, Yavorovsky O P, Paustovsky Y O, Esumi H, Minchenko O H
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine.
Ukr Biokhim Zh (1999). 2009 Jul-Aug;81(4):59-68.
The main goal of this work was investigation of the effect of methyl tertbutyl ether, ecologically dangerous chemical compound, on the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB-3) and vascular endothelial growth factor (VEGF) mRNA in different rat organs. Expression of PFKFB-3 and VEGF is a hypoxia inducible factor (HIF)-dependent process which significantly increases under hypoxia, in malignant tumors and other pathology. In this study we have shown that PFKFB-3 and VEGF mRNA expression in the liver, lung, and heart changes in rats, treated with methyl tertbutyl ether for two months, in organ-specific manner. Expression of alternative splice variants of PFKFB-3 mRNA as well as VEGF mRNA also changes in organ-specific manner in rats, treated with methyl tertbutyl ether. The effect of methyl tertbutyl ether on the expression of PFKFB-3 and VEGF mRNA and its alternative splice variants is dose-dependent. Results of this investigation clearly demonstrated that methyl tertbutyl ether affects the expression of PFKFB-3, a key regulatory enzyme of glycolysis, as well as VEGF, very important factor of angiogenesis, in an organ-specific and dose-dependent manner.
这项工作的主要目标是研究甲基叔丁基醚（一种具有生态危险性的化合物）对不同大鼠器官中6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶-3（PFKFB-3）和血管内皮生长因子（VEGF）mRNA表达的影响。PFKFB-3和VEGF的表达是一个依赖缺氧诱导因子（HIF）的过程，在缺氧、恶性肿瘤及其他病理状态下会显著增加。在本研究中，我们发现用甲基叔丁基醚处理两个月的大鼠，其肝脏、肺和心脏中PFKFB-3和VEGF mRNA的表达会以器官特异性方式发生变化。在用甲基叔丁基醚处理的大鼠中，PFKFB-3 mRNA以及VEGF mRNA的可变剪接变体的表达也以器官特异性方式发生变化。甲基叔丁基醚对PFKFB-3和VEGF mRNA及其可变剪接变体表达的影响呈剂量依赖性。本研究结果清楚地表明，甲基叔丁基醚以器官特异性和剂量依赖性方式影响糖酵解的关键调节酶PFKFB-3以及血管生成的重要因子VEGF的表达。
