In vivo and in vitro zinc (Zn) deficiency diminished T lymphocyte activity through the modulation of PKC isoenzymes

G A CREMASCHI; A J KLECHA; A ORQUEDA; M A KALISKI; M L BARREIRO ARCOS; M ZUBILLAGA; M WALD; A M GENARO

Miami, USA.

Congreso; 94 th Annual Meeting The American Association of Immunologists; 2007

The American Association of Immunologists, Inc.

Zn is essential to numerous signaling proteins that share Zn-finger structures as a common motif. It is crucial for immunocompetent cells, as its deficiency leads to immune function alterations. The exact mechanisms involved in Zn regulation of lymphocyte activity are still unclear. Here we analyzed both the direct and the in vivo effect of Zn deficiency on normal T cells and the involvement of protein kinase C (PKC) (an enzyme with cysteine-rich domains) and its isoenzyme profile. For this purpose mitogen stimulated normal T cells were cultured in the absence or presence of specific intra- or extracellular Zn chelators. These effects were compared with those obtained in mitogen-stimulated lymphocytes purified from mice fed with Zn deficient diets. Proliferation, PKC activity and the pattern of PKC isoenzymes were evaluated. Zn chelators inhibited normal cell proliferation and their effects were reverted by in vitro Zn addition. Similar effects were observed in lymphocytes from Zn deficient mice. In both experimental conditions, a decrease in PKC activity and in mitogen-induced translocation of the enzyme to cell membranes were observed. These effects were accompanied by a decrease in PKC and isoforms. These results show that Zn plays an important role in T cell growth and that its deficiency would alter the expression of key PKC isoenzymes that are essential signalling molecules involved in lymphocyte activation.