Minchenko O H, Garmash I A, Minchenko D O, Kuznetsova A Y, Ratushna O O
Ukr Biochem J. 2017 Jan-Feb;89(1):38-49. doi: 10.15407/ubj89.01.038.
We have studied the effect of hypoxia on the expression level of mRNA of the basic enzymes of pentose-phosphate cycle (G6PD, TKT, TALDO1, PGLS and RPIA) and glucose-6-phosphate isomerase (GPI) in U87 glioma cells in relation to inhibition of IRE1 (inositol requiring enzyme 1). It was shown that hypoxia leads to up-regulation of the expression of GPI and PGLS genes and to down-regulation of TALDO1 and RPIA genes in control glioma cells. Changes for GPI gene were more significant than for other genes. At the same time, inhibition of IRE1 modified the effect of hypoxia on the expression of all studied genes. In particular, it increased sensitivity to hypoxia of G6PD and TKT genes expression and suppressed the effect of hypoxia on the expression of GPI and RPIA genes. Additionally, inhibition of IRE1 eliminated hypoxic regulation of PGLS gene and did not change significantly effect of hypoxia on the expression of TALDO1 gene in glioma cells. Present study demonstrated that hypoxia, which often contributes to tumor growth, affects the expression of most studied genes and inhibition of IRE1 modified the hypoxic regulation of pentose-phosphate cycle gene expressions in a gene specific manner and thus possibly contributes to slower glioma growth, but several aspects of this regulation warrant further investigation.
我们研究了缺氧对U87胶质瘤细胞中磷酸戊糖途径基本酶（葡萄糖-6-磷酸脱氢酶、转酮醇酶、转醛醇酶1、6-磷酸葡萄糖酸脱氢酶和磷酸核糖异构酶A）以及葡萄糖-6-磷酸异构酶（GPI）mRNA表达水平的影响，以及与肌醇需要酶1（IRE1）抑制的关系。结果表明，在对照胶质瘤细胞中，缺氧导致GPI和6-磷酸葡萄糖酸脱氢酶基因表达上调，转醛醇酶1和磷酸核糖异构酶A基因表达下调。GPI基因的变化比其他基因更显著。同时，IRE1的抑制改变了缺氧对所有研究基因表达的影响。特别是，它增加了葡萄糖-6-磷酸脱氢酶和转酮醇酶基因表达对缺氧的敏感性，并抑制了缺氧对GPI和磷酸核糖异构酶A基因表达的影响。此外，IRE1的抑制消除了胶质瘤细胞中6-磷酸葡萄糖酸脱氢酶基因的缺氧调节，并且对缺氧对转醛醇酶1基因表达的影响没有显著改变。目前的研究表明，常促进肿瘤生长的缺氧影响了大多数研究基因的表达，IRE1的抑制以基因特异性方式改变了磷酸戊糖途径基因表达的缺氧调节，因此可能有助于减缓胶质瘤生长，但这种调节的几个方面值得进一步研究。
