Biopolym. Cell. 2008; 24(3):260-266.
http://dx.doi.org/10.7124/bc.0007A9
Short Communications
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase mRNA expression in streptozotocin-diabetic rats
1Mykhalchenko V. G., 2Tsuchihara K., 1Minchenko D. O., 2Esumi H., 3Prystupiuk O. M., 1Minchenko O. H.
  1. Palladin Institute of Biochemistry, NAS of Ukraine
    9, Leontovycha Str., Kyiv, Ukraine, 01601
  2. National Cancer Center Hospital East
    6-5-1 Kashiwanoha, Kashiwa-shi, Chiba 277-8577, Japan
  3. Bogomoletz Institute of Physiology, NAS of Ukraine
    4, Bogomolets Str., Kyiv, Ukraine, 01024

Abstract

We have determined that changes in the expression of 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase mRNA in streptozotocin-diabetic rats vary in different organs. The expression of different splice variants of PFKFB-3 mRNA is organ specific and changes in diabetes. We have identified new splice variant of PFKFB-3 mRNA which has catalytic domains identical to those of the main isoform and other alternative splice variants of PFKFB-3 but differs by the length of C-terminus. Results of this investigation support possible role of PFKFB-3 isozymes in adaptation of the cells to disordered carbohydrate metabolism resulting from the insulin deficiency.
Keywords: PFKFB-3 mRNA, alternative splicing, streptozotocin-diabetes, rats
Full text: (PDF, in English) (PDF, in Ukrainian)

References

[1] Rider MH, Bertrand L, Vertommen D, Michels PA, Rousseau GG, Hue L. 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis. Biochem J. 2004;381(Pt 3):561-79.
[2] Bando H, Atsumi T, Nishio T, Niwa H, Mishima S, Shimizu C, Yoshioka N, Bucala R, Koike T. Phosphorylation of the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase/PFKFB3 family of glycolytic regulators in human cancer. Clin Cancer Res. 2005;11(16):5784-92.
[3] Chesney J. 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and tumor cell glycolysis. Curr Opin Clin Nutr Metab Care. 2006;9(5):535-9.
[4] Atsumi T, Nishio T, Niwa H, Takeuchi J, Bando H, Shimizu C, Yoshioka N, Bucala R, Koike T. Expression of inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase/PFKFB3 isoforms in adipocytes and their potential role in glycolytic regulation. Diabetes. 2005;54(12):3349-57.
[5] Wu C, Khan SA, Peng LJ, Li H, Carmella SG, Lange AJ. Perturbation of glucose flux in the liver by decreasing F26P2 levels causes hepatic insulin resistance and hyperglycemia. Am J Physiol Endocrinol Metab. 2006;291(3):E536-43.
[6] Wu C, Okar DA, Newgard CB, Lange AJ. Increasing fructose 2,6-bisphosphate overcomes hepatic insulin resistance of type 2 diabetes. Am J Physiol Endocrinol Metab. 2002;282(1):E38-45.
[7] Rousseau GG, Hue L. Mammalian 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: a bifunctional enzyme that controls glycolysis. Prog Nucleic Acid Res Mol Biol. 1993;45:99-127.
[8] Okar DA, Manzano A, Navarro-Sabate A, Riera L, Bartrons R, Lange AJ. PFK-2/FBPase-2: maker and breaker of the essential biofactor fructose-2,6-bisphosphate. Trends Biochem Sci. 2001;26(1):30-5.
[9] Okar DA, Lange AJ. Fructose-2,6-bisphosphate and control of carbohydrate metabolism in eukaryotes. Biofactors. 1999;10(1):1-14.
[10] Kawaguchi T, Veech RL, Uyeda K. Regulation of energy metabolism in macrophages during hypoxia. Roles of fructose 2,6-bisphosphate and ribose 1,5-bisphosphate. J Biol Chem. 2001;276(30):28554-61.
[11] Minchenko A, Leshchinsky I, Opentanova I, Sang N, Srinivas V, Armstead V, Caro J. Hypoxia-inducible factor-1-mediated expression of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) gene. Its possible role in the Warburg effect. J Biol Chem. 2002;277(8):6183-7.
[12] Minchenko O, Opentanova I, Minchenko D, Ogura T, Esumi H. Hypoxia induces transcription of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 gene via hypoxia-inducible factor-1alpha activation. FEBS Lett. 2004;576(1-2):14-20.
[13] Hopfl G, Ogunshola O, Gassmann M. HIFs and tumors--causes and consequences. Am J Physiol Regul Integr Comp Physiol. 2004;286(4):R608-23.
[14] Lu H, Forbes RA, Verma A. Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem. 2002;277(26):23111-5.
[15] Minchenko O, Opentanova I, Caro J. Hypoxic regulation of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene family (PFKFB-1-4) expression in vivo. FEBS Lett. 2003;554(3):264-70.
[16] Navarro-Sabate A, Manzano A, Riera L, Rosa JL, Ventura F, Bartrons R. The human ubiquitous 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene (PFKFB3): promoter characterization and genomic structure. Gene. 2001;264(1):131-8.
[17] Hirata T, Kato M, Okamura N, Fukasawa M, Sakakibara R. xpression of human placental-type 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase in various cells and cell lines. Biochem Biophys Res Commun. 1998;242(3):680-4.
[18] Chesney J, Mitchell R, Benigni F, Bacher M, Spiegel L, Al-Abed Y, Han JH, Metz C, Bucala R. An inducible gene product for 6-phosphofructo-2-kinase with an AU-rich instability element: role in tumor cell glycolysis and the Warburg effect. Proc Natl Acad Sci U S A. 1999;96(6):3047-52.
[19] Atsumi T, Chesney J, Metz C, Leng L, Donnelly S, Makita Z, Mitchell R, Bucala R. High expression of inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (iPFK-2; PFKFB3) in human cancers. Cancer Res. 2002;62(20):5881-7.
[20] Watanabe F, Sakai A, Furuya E. Novel isoforms of rat brain fructose 6-phosphate 2-kinase/fructose 2,6-bisphosphatase are generated by tissue-specific alternative splicing. J Neurochem. 1997;69(1):1-9.
[21] Kessler R, Eschrich K. Splice isoforms of ubiquitous 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in human brain. Brain Res Mol Brain Res. 2001;87(2):190-5.
[22] Wu C, Okar DA, Newgard CB, Lange AJ. Overexpression of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase in mouse liver lowers blood glucose by suppressing hepatic glucose production. J Clin Invest. 2001;107(1):91-8.
[23] Duran J, Navarro-Sabate A, Pujol A, Perales JC, Manzano A, Obach M, Gomez M, Bartrons R. Overexpression of ubiquitous 6-phosphofructo-2-kinase in the liver of transgenic mice results in weight gain. Biochem Biophys Res Commun. 2008;365(2):291-7.
[24] Minchenko AG, Stevens MJ, White L, Abatan OI, Komjati K, Pacher P, Szabo C, Obrosova IG. Diabetes-induced overexpression of endothelin-1 and endothelin receptors in the rat renal cortex is mediated via poly(ADP-ribose) polymerase activation. FASEB J. 2003;17(11):1514-6.
[25] Obrosova IG, Minchenko AG, Frank RN, Seigel GM, Zsengeller Z, Pacher P, Stevens MJ, Szabo C. Poly(ADP-ribose) polymerase inhibitors counteract diabetes- and hypoxia-induced retinal vascular endothelial growth factor overexpression. Int J Mol Med. 2004;14(1):55-64.
[26] Drogat B, Auguste P, Nguyen DT, Bouchecareilh M, Pineau R, Nalbantoglu J, Kaufman RJ, Chevet E, Bikfalvi A, Moenner M. IRE1 signaling is essential for ischemia-induced vascular endothelial growth factor-A expression and contributes to angiogenesis and tumor growth in vivo. Cancer Res. 2007;67(14):6700-7.
[27] Riera L, Manzano A, Navarro-Sabate A, Perales JC, Bartrons R. Insulin induces PFKFB3 gene expression in HT29 human colon adenocarcinoma cells. Biochim Biophys Acta. 2002;1589(2):89-92.
[28] Duran J, Gomez M, Navarro-Sabate A, Riera-Sans L, Obach M, Manzano A, Perales JC, Bartrons R. Characterization of a new liver- and kidney-specific pfkfb3 isozyme that is downregulated by cell proliferation and dedifferentiation. Biochem Biophys Res Commun. 2008;367(4):748-54.
[29] Wu C, Okar DA, Kang J, Lange AJ. Reduction of hepatic glucose production as a therapeutic target in the treatment of diabetes. Curr Drug Targets Immune Endocr Metabol Disord. 2005;5(1):51-9.