NHE1 HYPERACTIVITY IN AN IN VITRO MODEL OF DIABETES

CAROLINA JAQUENOD DE GIUSTI; PAULA AYELEN LAMAS; RAYEN DE FAZIO

Mar del Plata

Congreso; Reunión Conjunta SAIC SAI SAFIS 2018; 2018

SAIC, SAI,SAFIS

Diabetes mellitus (DM) is a disease of growing incidence worldwide and is a significant risk factor for cardiovascular disease. In the heart, intracellular pH (pHi) influences cardiac functionality and its dysregulation is related to various cardiac pathologies. For pHi regulation, several ion transporters intervene, among which is the Na + / H + exchanger (NHE1). Although NHE1 normally plays an important physiological role, aberrant regulation and overactivation of NHE1 contribute to heart disease, including acute ischemia reperfusion damage and cardiac hypertrophy. NHE1 hyperphosphorylation, exaggerated myocyte hypertrophy and apoptotic death was observed in human diabetic ischemic cardiomyopathy.We aim to dissect the mechanism of NHE1 hyperactivity in diabetic heart using an in vitro model of diabetic cardiomyopathy. Rat myoblast H9C2 cells were treated with a medium that mimics diabetic patient?s plasma, that is, increased free fatty acids (FFA) and high glucose (HG). Cells were cultured and treated with a low glucose (LG) medium for 24 hs and then changed to a HG and/or high palmitate(HP) medium. While NHE1 expression levels did not change in any of the conditions tested, NHE1 activity was increased in cells treated with HG, HP and HGHP, showing that both metabolites could be related to the increased NHE1 activity. Considering that NHE1 expression levels remained unchanged, maybe the mechanism involved could be NHE1 phosphorylation. Further studies using kinaseinhibitors will help to probe this hyphotesis.