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

MORA SANDRA; OLIVERI LEDA; PARERA VICTORIA ESTELA; ROSSETTI MARÍA VICTORIA; GEREZ, ESTHER

Mar del Plata, Buenos Aires - Argentina

Congreso; LXI REUNION CIENTIFICA ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION CLINICA (SAIC),; 2016

Sociedad Argentina de Investigación Clínica

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 (IGF1) has any rol 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 DMEN 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  subunit of IGF1 receptor. Control cells were treated with the corresponding vehicle.According the results on these levels they were divided in three groups: normal IGF1 and ALA; low IGF1 and high ALA; normal IGF1 and high ALA. Referemce values: IGF1 values depends on the age (ng/ml); ALAS  4mg/24h. In the population studied 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. This results would suggest a significative role of IGF1 on ALAS1 expression levels.