Expression of 6-phosphofructo-2-kinase/ fructose-2,6-bisphosphatase-3 and VEGF mRNA in rat liver, lung and heart: effect of methyl tertbutyl ether.
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.
Minchenko
D O
DO
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine. ominchenko@yahoo.com
Kundieva
A V
AV
Tsuchihara
K
K
Yavorovsky
O P
OP
Paustovsky
Y O
YO
Esumi
H
H
Minchenko
O H
OH
D017398:Alternative Splicing; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000633:toxicity*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D009928:Organ Specificity; D025481:Phosphofructokinase-2 / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
D004785:Environmental Pollutants; D008738:Methyl Ethers; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C043243:methyl tert-butyl ether; D025481:Phosphofructokinase-2