Interrelation between intracellular Calcium and pHi changes upon voltage-gated Proton channel hv1 inhibition in tumoural and Non-tumoural human t lymphocytes.

A ASUAJE; DI MATTIA R; C VENTURA; FARIS P; AIELLO A; MONTAGNA D; MOCCIA F; V MILESI

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argetina de Investigaciones Clínicas (SAIC); 2018

Sociedad Argentina de Investigaciones Clínicas (SAIC)

It is widely known that cytoplasmic calcium dynamics play an importantrole in cellular processes key for tumour development suchas pro-proliferative signaling, migration, proliferation, and tumourigenesis.On the other hand, increased metabolic rates and thepathways rewiring (known as Warburg effect) lead to an intracellularoverproduction of acidic species that must be extruded in orderto maintain cellular viability. Thus, targeting proton transportershas arisen as a promising strategy in experimental oncology. Fromthose, the voltage-gated proton channel Hv1 represent a singularpassive pathway for extrusion being scarcely studied compared withother structures (NHE1, CA, MCTs, etc.). We found that Hv1 inhibitorCl-GBI induces an immediate pH decrease in leukemic Jurkat Tcells independently of extracellular Na+ availability (-0,11±0,01 w/oNa+e p=0,02; -0,05±0,02 w/ Na+e p=0,04). As intracellular acidificationmay have several consequences, including calcium transporters activity, in this work we tested the effect of Cl-GBI inducedacidification on cytoplasmic calcium levels ([Ca2+]c). This derivedin a sustained [Ca2+]c increase in both Jurkat and non-tumouralT cells being considerably higher in the former ones (0.116±0.009p