FoxO1 target genes are altered in the heart of the offspring from diabetic rats

SABRINA LORENA ROBERTI; ALICIA JAWERBAUM; HUGO SATO; ROMINA HIGA

Buenos Aires

Congreso; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC), Buenos Aires, Noviembre de 2017; 2017

SAIC

Cardiovascular alterations in the adult can be developmentally programmed by maternal diabetes. FoxO1 participates in cellular oxidative homeostasis, metabolism and survival of cardiomyocites and its overactivation is related with cardiac dysfunction in diabetes. We have previously found increased FoxO1 levels in the offspring?s heart from diabetic rats. FoxO1 activation can be inhibited by serum glucocorticoid kinase 1 (sgk1) phosphorylation that induces FoxO1 nuclear exportation. Connective tissue growth factor (CTGF, regulates fibrosis) and MMP2 (related to inflammatory processes when it is in excess) are FoxO1 target genes. Our objective is to evaluate serum markers of heart damage, mRNA levels of CTGF and MMP2 and phosphorylation status of sgk1 in the heart?s offspring from control and diabetic rats. Methodology: Pregestational diabetic rats were obtained by neonatal streptozotocin administration and were mated with healthy males. Adult male offspring from control and diabetic rats were evaluated. Serum levels of lactate dehydrogenase (LDH) and myocardium creatine kinase (CK-MB) were determined by a commercial kit. In the heart, CTGF and MMP2 mRNA levels were evaluated by qPCR and phosphorylation status of sgk1 by western blot. Results: LDH and CK-MB, serum markers of heart damage, were found increased in diabetic offspring compared to control (1.8 and 1.5 fold, p