tailieunhanh - Báo cáo khoa học: Pfkfb3 is transcriptionally upregulated in diabetic mouse liver through proliferative signals

The ubiquitous isoform of 6-phosphofructo-2-kinase⁄fructose-2,6-bisphos-phatase (uPFK-2), a product of thePfkfb3gene, plays a crucial role in the control of glycolytic flux. In this study, we demonstrate that Pfkfb3gene expression is increased in streptozotocin-induced diabetic mouse liver. The Pfkfb3⁄-3566 promoter construct linked to the luciferase reporter gene was delivered to the liver via hydrodynamic gene transfer. | ỊFEBS Journal Pfkfb3 is transcriptionally upregulated in diabetic mouse liver through proliferative signals Joan Duran1 Merce Obach1 Aurea Navarro-Sabate1 Anna Manzano1 Marta Gomez1 Jose L. Rosa1 Francesc Ventura1 Jose C. Perales2 and Ramon Bartrons1 1 Unitat Bioquimica i Biologia Molecular Universitat de Barcelona Spain 2 Unitat de Biofisica Departament de Ciencies Fisiologiques I DIBELL Universitat de Barcelona Spain Keywords 6-phosophofructo-2-kinase fructose-2 6-bisphosphatase diabetes fructose-2 6-bisphosphate liver streptozotocin Correspondence R. Bartrons Unitat Bioquimica i Biologia Molecular Universitat de Barcelona Feixa Llarga s n E-08907 L Hospitalet Barcelona Spain Fax 34934024268 Tel 34934024252 E-mail rbartrons@ These authors contributed equally to this work Received 3 April2009 revised 12 June 2009 accepted 17 June 2009 doi The ubiquitous isoform of 6-phosphofructo-2-kinase fructose-2 6-bisphos-phatase uPFK-2 a product of the Pfkfb3 gene plays a crucial role in the control of glycolytic flux. In this study we demonstrate that Pfkfb3 gene expression is increased in streptozotocin-induced diabetic mouse liver. The Pfkfb3 -3566 promoter construct linked to the luciferase reporter gene was delivered to the liver via hydrodynamic gene transfer. This promoter was upregulated in streptozotocin-induced diabetic mouse liver compared with transfected healthy cohorts. In addition increases were observed in Pfkfb3 mRNA and uPFK-2 protein levels and intrahepatic fructose-2 6-bisphos-phate concentration. During streptozotocin-induced diabetes phosphorylation of both p38 mitogen-activated protein kinase and Akt was detected together with the overexpression of the proliferative markers cyclin D and E2F. These findings indicate that uPFK-2 induction is coupled to enhanced hepatocyte proliferation in streptozotocin-induced diabetic mouse liver. Expression decreased when hepatocytes were treated with either rapamycin or LY .