Histamine modulates cell growth reactive-oxygen species production and activity of antioxidants enzymes in human cell lines.

MEDINA VANINA; CRICCO GRACIELA; GARBARINO GLORIA; NUÑEZ MARIEL; MARTIN GABRIELA; COCCA CLAUDIA; BERGOC ROSA; RIVERA ELENA

Diciembre 5-8, 2004, Iguazú, Misiones, Argentina.

Congreso; XL Reunión de la Sociedad Argentina de Investigaciones Bioquímicas,; 2004

Histamine modulates CELL GROWTH, reactive oxygen species production  AND ACTIVITY OF ANTIOXIDANT ENZYMES IN HUMAN CELL LINES  V. Medina, G. Cricco, G.Garbarino, M. Núñez, G. Martín, C. Cocca, R. M. Bergoc, E.S. Rivera. Lab Radioisotopos, Fac. Farmacia y Bioquímica, UBA,. E-mail: vmedina@ffyb.uba.ar In the present work  we investigated the capacity of Histamine (HA) to modulate cell proliferation and ROS production as well as the receptors involved in this response. We employed mammary normal (HBL-100) and malignant cell lines (MDA-MB-231, MCF-7). The levels of the free radicals superoxide (O2·-) and hydrogen peroxide (H2O2) and intracellular HA content were determined by flow citometry. The activity of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) were determined by kinetic spectrophotometric techniques. Cell proliferation was evaluated by the clonogenic assay. Cell lines presented intracellular levels of HA directly correlated with their malignancy. In MDA-MB-231, HA via H2R increased camp levels (EC50 0.45 mm) producing in turn a significant inhibition on cell proliferation (p<0.01). On the contrary, HA at low doses (<0,1 mm)  and via H1R, stimulated cell growth. H2O2 levels resulted inversely correlated with cell proliferation while O2·- remained unchanged. Furthermore, HA significantly modified the activity of SOD and CAT. In normal HBL-100, HA modulated cell proliferation but in exactly the opposite range of doses. The effect on cell growth was inversely correlated with H2O2 levels. The present data indicate that histamine can modulate cell proliferation via H1R and H2R. This effect is exerted in part by the modulation of antioxidant enzymes and ROS production.