Effect of Vanadate on 5-Aminolevulinic Synthetase in a Murine Model of Acute Intermittent Porphyria

RUSPINI, SILVINA; BATLLE ALCIRA; ZUCCOLI, JOHANNA; MORA, SANDRA; OLIVERI, LEDA; BUZALEH ANA MARIA; MARTINEZ MARIA DEL CARMEN; GEREZ ESTHER

BURDEOS

Congreso; ICPP Porphyrins and Porphyrias 2017; 2017

INTERNATIONAL CONGRESS OF PORPHYRINS AND PORPHYRIAS

Acute Intermittent Porphyria (AIP) is characterized by an reduced activity of Porphobilinogen deaminase (PBG-D), increased levels of the first and rate limiting enzyme of heme pathway, 5-Aminolevulinic synthetase (ALA-S) and the accumulation of neurotoxic precursors, ALA and porphobilinogen. ALA-S can be induced by fasting or chemical agents. We have demonstrated that vanadate prevents the transcriptional increase of ALA-S in a murine model of diabetes. The aim of this study was to investigate the effect of vanadate on ALA-S in a murine model of AIP. Male and female knockout PBG-D deficient mice (Pbgd-/-) were divided in three experimental groups: non-fasted controls (C), fasted 24 hours (F) and vanadate (0.3 mg/ml in drinking water)+fasted (V+F). V was administered during 16 or 21 days. A significant lost of body weight was observed in males of F and V+F groups respect to C group, this effect was not produced in females. Starvation increased the activity (100-500%, p