Zinc deficiency induced T lymphocyte apoptosis involving caspase 3 activation and decreased levels of PKC isoforms

STERLE H.A.; PAULAZO M.A.; KLECHA A.J.; BARREIRO ARCOS M.L.; CREMASCHI G.A.

Sociedad Iberoamericana de Neuroinmunomodulación

Congreso; III Iberoamerican Congress on Neuroimmunomodulation.; 2009

Sociedad Iberoamericana de Neuroinmunomodulación

Zinc (Zn) regulates T lymphocyte physiology and its deficiency leads to lymphocyte apoptosis, although the biochemical mechanisms involved have not been elucidated. We here analyze the intracellular events related to Zn deficiency in normal T lymphocyte (LTN) and BW 5147 T lymphoma cells (BW), that are regulated by different signaling molecules. Both extra- and intracellular Zn chelators were able to inhibit LTN and BW division leading to apoptosis. This was a accompanied by an increase in reactive oxygen species. Both effects were reverted by the addition of Zn and of a precursor of glutathione, N-acetyl-L-cysteine. Both chelators induced mitochondrial damage. The participation of protein kinase C (PKC), a crucial enzyme in T lymphocytes activity that utilized Zn as a cofactor, was evaluated. Zn chelators inhibit PKC activation on LTN and BW cells. Additionally, Zn chelators diminished PKC isoform protein expression, with a decrease in a on both cell types and z on BW cells. Also chelators induce the activation of caspase 3 on LTN and BW. Results indicate that Zn deficiency-induced apoptosis in T lymphocytes through the decreased levels of specific PKC isoenzymes, probably related to the activation of caspase 3, leading to mitochondrial damage and cell death.