EFFECT OF METHYL TERTIAL BUTYL ETHER ON THE EXPRESSION OF mRNA CODING FOR 6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE-2,6-BISPHOSPHATASE-3 AND VEGF IN RAT LIVER AND LUNG
DOI: http://dx.doi.org/10.30970/sbi.0302.038
Abstract
Methyl tertial butyl ether, an oxygenated compound of gasoline, is a toxic and ecologically dangerous chemical compound with an ability to introduce a variety of neurotoxic, allergic and respiratory diseases, as well as cancer and leukemia. We used RT/PCR or quantitative PCR to study the effect of methyl tertial butyl ether (everyday injection for one month) on the expression of mRNA coding for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB-3) and vascular endothelial growth factor (VEGF), which are important for tumor growth and metastasis in the lung and liver. The level of PFKFB-3 and VEGF mRNA expression was increased in the liver in methyl tertial butyl ether treated rats with respect to the control animals. However, methyl tertial butyl ether had opposite effect on the expression of PFKFB-3 and VEGF mRNA in the lung: with strong induction of PFKFB-3 and suppression of VEGF mRNA expression. Moreover, alternative splicing of PFKFB-3 mRNA was changed in methyl tertial butyl ether treated rats in organ specific manner. Thus, methyl tertial butyl ether induces alternative splicing of PFKFB-3 mRNA accompanied by appearing of variants with longer C-terminus in the liver, and with shorter C-terminus in the lung. The results of this investigation clearly demonstrate that methyl tertial butyl ether affects in organ-specific manner the expression and alternative splicing of mRNA coding for PFKFB-3 and VEGF, key regulatory factors of glycolysis, and angiogenesis.
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