Ferrochelatase expression in a murine model of diabetes mellitus type I

OLIVERI, LEDA; MEISS, ROBERTO; BATLLE, ALCIRA; GEREZ, ESTHER

Newport, Rhode Island, Estados Unidos

Congreso; GORDON RESEARCH CONFERENCE ON THE CHEMISTRY AND BIOLOGY OF TETRAPYRROLES; 2006

Gordon Research Conferences

Diabetes causes changes in the metabolism of hemeproteins, probably due to the alterations of hepatic enzymes involved in heme biosynthesis.  Ferrochelatase (FQ), the enzyme involved in  the last step of this pathway, catalyzes the chelation of ferrous ion into protoporphyrin IX to form protoheme. The aim of this study was to examine the transcription of hepatic FQ in a murine streptozotocin (STZ)-induced diabetes model. Animals were diabetized with a single dose of STZ, 170 mg/kg i.p), diabetic onset was confirmed by assessing blood and urine glucose levels 16 days after STZ injection. The expression of FQ mRNA increased immediately after the onset of diabetes reaching a maximum induction on day 8. This enhancement was maintained throughout the whole period od the experiment (26 days). Vanadate, a well-known insulin mimetic agent, when given at 0.2 mg/ml in drinking water, abolished both hyperglicemia and FQ mRNA induction caused by STZ. Since the 5’-regulatory region of mouse FQ gene contains Sp1 sites involved in transcription activation, we measured both Sp1 and Sp1 glycosylation levels in animals treated with STZ and STZ plus Vanadate. As assessed by Western blotting, we demonstrated that Sp1 and Sp1 O-glycosilated augmented in liver of diabetic animals, whereas vanadate impaired both overexpression and hyperglycosilation of Sp1. These results suggest that Sp1 might be involved in the changes of FQ expression caused by diabetic status.