| 12203019 |
Reiter TA, Rusnak F: Is calcineurin a peroxide-specific sensor in T-lymphocytes? . J Biol Inorg Chem. 2002 Sep;7(7-8):823-34. Epub 2002 May 14.
Calcineurin activity in T-lymphocytes has been shown to be sensitive to H (2) O (2). In this report, we investigate the effects of H (2) O (2) and other physiological oxidants on calcineurin activity both in vivo and in vitro. Intracellular calcineurin activity, as determined by NF-AT phosphorylation state and activity, is inhibited by H (2) O (2) but is insensitive to superoxide and NaOCl. Similarly, treatment of T-lymphocytes with NaOCl and paraquat does not drastically alter the activity of calcineurin in crude cell lysate, while H (2) O (2) causes significant inhibition. Sensitivity to H (2) O (2) and NaOCl in vivo correlates with the half-life of each species in cell medium. The intracellular redox potential is unaffected by H (2) O (2) (100 micro M) or NaOCl (600 micro M), indicating that H (2) O (2) inhibits calcineurin via a direct mechanism that does not involve a change in the cytosolic redox potential. In contrast, calcineurin activity in cell lysate is inhibited by all three oxidants. H (2) O (2) inactivation of calcineurin is rapid, with inactivation occurring in inactivation of calcineurin is reversible in T-lymphocyte lysate using dithiothreitol (DTT) alone, while in rat brain lysate, reversibility requires both DTT and Fe (II), implicating that the enzyme may exist in different metal/redox-sensitive states in different tissues. |
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