ALTERATION OF T LYMPHOCYTE ACTIVITY BY ZINC DEFICIT INVOLVES DIFFERENTIAL MODULATION OF PKC ISOENZYMES

ANDRÉS ORQUEDA; MARÍA LAURA BARREIRO ARCOS; MIRIAM RUTH WALD; ANA MARÍA GENARO; GRACIELA ALICIA CREMASCHI

Mar del Plata

Congreso; XXXVII Reunión anual de Sociedad Argentina de Farmacología Experimental; 2005

Sociedad Argentina de Farmacología Experimental

 Zinc (Zn) is essential to the structure of numerous signaling proteins that share zinc-finger structures as a common motif  and is known to be essential for all highly proliferating cells, especially those from the immune system. The aim of this study was to analyze the direct effect of  Zn deficiency on normal T lymphocyte cultures and to ascertain the role that protein kinase C (PKC), an enzyme containing cysteine-rich domains, and its isoenzyme profile play in these actions. For this purpose addition of the intra-(TPEN) or extracellular (DTPA) specific zinc chelators in murine mitogen-induced normal T cell proliferation was studied by [3H]-thymidine incorporation. Both TPEN and DTPA exerted dose-response inhibition of normal T cell proliferation and viability, that was reversed by previous incubation of the chelator with adequate Zn concentrations. Zn chelators significantly diminished PKC activity in normal T lymphocytes as measured by 32P-phosphorylation of specific substrates. When analyzing PKC isoenzyme expression by western blot, a decrease in conventional a and novel q PKC was observed in TPEN-treated normal T cells respect to control, that was reverted by Zn preincubation of the chelator. Moreover an increment in atypical PKC z isoform was also found. As both PKC a and q are essential signalling molecules for normal T lymphocyte activity, diminished expression of these isoform would be related with inhibiton of mitogen-induced proliferation of normal T lymphocytes. Increment in PKC z would probably reflect a mechanism to avoid cellular death in still surviving cells.