The effect of insulin growth factor 1 on delta-aminolevulinic synthase expression

MORA SANDRA MILENA; OLIVERI LEDA; BATLLE ALCIRA; PARERA VICTORIA; ROSSETTI MARIA VICTORIA; GEREZ ESTHER

Congreso; LXI REUNION CIENTIFICA ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIONES CLINICAS; 2016

Acute Intermittent Porphyria (AIP) is an inherited disorder of heme biosynthesis characterized by a reduced activity of Porphobilinogen-deaminase, associated to a marked increase in the expression of the hepatic isoform of delta-aminolevulinic synthase (ALAS1), the first and regulatory enzyme of the pathway, with the accumulation of the neurotoxic precursor ALA.The aim of this study was to investigate if the insulin like growth factor 1 (IGF1) has any role on ALAS1 regulation.IGF1 levels in plasma and ALA levels in urine in 50 AIP patients were determined. In the in vitro assays C3A cells were incubated in DMEM medium and treated with IGF1 for 15min at different concentrations (1, 10, 50 nM), in the presence and absence of AG1024/L, a selective inhibitor of the tyrosine fosforilation of the beta subunit of IGF1 receptor. Control cells were treated with the corresponding vehicle.According to these results patients were divided in three groups: normal IGF1 and ALA; low IGF1 and high ALA; normal IGF1 and high ALA. Reference values: IGF1 values depend on the age (ng/ml); ALAS lower than 4mg/24h. In the studied population a significant correlation was observed in the group with low IGF1 and high ALA levels (p  0.001). In vitro assays, IGF1 treatment leads to a reduction of 61% in the ALAS1 mRNA basal levels; this effect was reversed by AG1024/L presence. These results would suggest a significant role of IGF1 on ALAS1 expression levels.