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.

Buenos Aires

Congreso; III Iberoamerican Congress of Neuroinmunomodulation; 2009

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 lymphocytes (LTN) and BW5147 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 accompanied by an increase in reactive oxygen species. Both effects were reverted by the addition of Zn and of a precursor of glutathione, the N-acetyl-cysteine. Both chelators induced mitochondrial damage. The participation of protein kinase C (PKC), a crucial enzyme in T lymphocyte activity that utilized Zn as a cofactor, was evaluated. Zn chelators inhibit PKC activation on LTN and BW. Additionally, Zn chelators diminished PKC isoform protein expression, with a decrease in α on both cell types, but of θ only on LTN and β1 and ζ 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 relates to the activation of caspase 3, leading to mitochondrial damage and cell death.