CytosolicCa2+ dynamics in normal and pathological human cells.

VIGIL M; ONTIVEROS M; RINALDI DE; ESPELT M.V; MANGIALAVORI I; REY O; ROSSI, JP; FERREIRA-GOMEZ MS

Congreso; Sociedad Argentina de Biofísica; 2018

Calcium homeostasis is highly regulated in cells. Free cytosolicCa2+([Ca2+]c), which acts as a second messenger, is crucial for a wide range of biological functions. All cells must maintain a low concentration of [Ca2+]c(~100 nM) to maintain viability, while using their increase as a versatile signaling pathway. Prolonged intracellular elevation of Ca2 + can trigger cell death. Evidence shows that the calcium homeostasis is altered in cancer cells and the alteration is involved in tumor onset, angiogenesis, progression and metastasis. In this work, we characterized the dynamics of [Ca2+]cfor different neoplastic lines SW480, CaCo and HepG2, and compare them with the normal dynamics of HEK293T cells.The dynamics of [Ca2+]cwereexamined by the Ca2+release from endoplasmic reticulum (ER) in the different cell lines. The cellswere loaded with fluo4 or fura2 to measure [Ca2+]cand followed the fluorescence in real timebefore and after the addition of thapsigargin, an inhibitor of the sarcoplasmic reticulum calcium pump. The dynamics of [Ca2+]cin HEK293T cells showed a maximum peak followed by an exponential decrease to the basal level. On the other hand,in the colon carcinoma cells,SW480 and CaCo,the peaks returned to a higher steady-state. In HepG2 cells, no peaks were observed but an exponential increase to a maximal steady-state.Then, we studied the effect of quercetin on the dynamics of [Ca2+]c. Quercetin is a flavonoid with antitumoral properties, which inhibits calcium channels and pumps, altering the intracellular calcium homeostasis. We observed that quercetin altered the dynamics of [Ca2+]c in SW480, CaCo, andHepG2 cells, whereas in HEK293T cells didnot change.Ours results suggest that quercetin could affect the calcium homeostasisin pathogenic cells by inhibition of Ca2+ transport systems.This work reveals that the study of dynamics of [Ca2+]ccould be used forcharacterizingdifferences in calcium homeostasis in pathogenic cells.