The role of calcium ions in the regulation of rat thymocyte pyruvate oxidation by mitogens

Abstract

Ca2+ concentrations in the nanomolar range cause a specific stimulation of pyruvate oxidation by isolated mitochondria from rat thymus. This was sufficient to account for pyruvate oxidation stimulation observed when rat thymocytes are incubated with the mitogens concanavalin A or ionophore A23187. Higher concentrations of Ca2+ (more than 50 nM) inhibit the oxidation of NAD+-linked substrates by rat thymus mitochondria without affecting the oxidation of succinate or ascorbate + NNN''N''-tetramethyl-p-phenylenediamine. The addition of Ni2+ or Co2+ (2 mM) to rat thymocytes prevented the response to concanavalin A at the pyruvate oxidation level without affecting the stimulation of glycolysis induced by this mitogen. The complete metabolic response to the ionophore A23187 was abolished by these ions. Ni2+ and Co2+ interfered with the ability of the ionophore to transport Ca2+ across the plasma membrane. Concanavalin A, but not ionophore A23187, increased the respiratory inhibition induced by Ni2+ and Co2+. The view that mitogens stimulate lymphocyte pyruvate oxidation through an increase in cellular Ca2+ uptake is supported.