Differential lymphocyte growth-modifying effects of oxidants: changes in cytosolic Ca+2
Abstract
An increase in the concentration of cytosolic Ca+2 ([Ca-2]i) is among the earliest changes seen in mitogen-stimulated lymphocytes and is a consequence of signal transduction which usually results in the initiation of cell cycle progression. However, increased [Ca+2]i has also been correlated with cytotoxicity. We have determined whether modulations of [Ca+2]i are involved in the functional inactivation of cells observed with sublethal concentrations of oxidants. Specifically, [Ca+2]i was measured in mouse splenic lymphocytes that were treated with different oxidants in order to determine if oxidative stress interferes with mitogen-stimulated increases in [Ca+2]i, if oxidants themselves modulated [Ca+2]i, and, if so, whether such Ca+2 modulations by oxidants had stimulatory or inhibitory effects on the response of lymphocytes to mitogens. The oxidants employed were copper phenanthroline (CuP; surface thiol oxidizer), N-ethyl maleimide (NEM; permeant thiol alkylator), hydrogen peroxide (H2O2; generates hydroxyl radical within the cell), and radiation (Cs137; generates hydroxyl radical by radiolysis). Growth of all treated cells was equally inhibited upon stimulation with Con A or PMA/A23187, suggesting that all the oxidants inhib...Continue Reading
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On the role of thiol groups in the inhibition of liver microsomal Ca2+ sequestration by toxic agents
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