Proliferative activity related to ß-adrenergic-mediated stimulation of protein kinase C and nitric oxide synthase on a T lymphoma.

MARÍA LAURA BARREIRO ARCOS, GABRIELA GORELIK, ALICIA KLECHA, GRACIELA CREMASCHI.

Edimburgo, Escocia

Congreso; VI Congress of the INternational Society of Neuroinmunology; 2001

International Society of Neuroinmunology

Low numbers of ß-adrenergic receptors (ßAR),  uncoupled to adenylate cyclase and positively modulated by inhibiting proliferative intracellular signals, were described in BW5147 T lymphoma cells. We here analyze protein kinase C (PKC) activity and its isoform pattern in ßAR modulation of BW5147 proliferation. PKC enzymatic activity and isozymes expression were  determined on both tumor and normal  or  mitogen-activated  T lymphocytes. Tumor  lymphocytes  showed  higher levels of translocated PKC than normal or stimulated T cell.  Also, different distribution of  PKC isoforms was detected, with tumor cells showing higher expression of atypical  isoforms, while normal and activated T lymphocytes expressing higher levels of calcium-dependent PKC isozymes. Furthermore, high levels of nitric oxide synthase (NOS) activity were found in BW5147 cells, despite no detectable activities were found in normal and mitogen-stimulated T cells. Elevated NOS and proliferative activities in tumor cells were impaired by PKC inhibitors and by L- NAME. The ß-adrenergic agonist isoproterenol was able to stimulate PKC, NOS and proliferative activities on tumor lymphocytes, effects that were blunted by ß antagonists.  In conclusion, the differential activity and isoenzyme distribution of PKC, related to high NOS activity, would protect BW5147 cells from negative selection. Decreased ßAR sites in these cells, coupled to positive signals for cellular activity, would contribute to stablish  a hyperproliferative state.    Supported by Ministerio de Salud.