Involvement of protein kinase C-ɛ in glucocorticoid-induced apoptosis in thymocytes

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Abstract
Apoptosis is induced in immature thymocytes by physiological peak levels of glucocortlcold hormones, especially in murine and rat cells. Endogenous glucocortlcolds may have some role in thymic selection. Glucocorticold-lnduced thymocyte apoptosis appears to be dependent on protein kinase C (PKC), since it is inhibited by PKC inhibitors. PKC Is a family of closely related enzymes, consisting of Ca2+-dependent (PKC-α, -βI, -βII, and ∼γ) and Ca2+-Independent (PKC-α, -β, (L), -Θ, -, and -λ) isozymes. In the present study, we analyzed the role of PKC in glucocorticold-lnduced apoptosis in murine thymocytes and found that glucocorticold selectively induces an increase in Ca2+ -Independent PKC activity in the paniculate fraction of Immature thymocytes but not in that of mature T cells. The increase as well as the apoptosis was inhibited by actlnomycln D, cyclohexlmkte, or the glucocortteoid receptor antagonist, RU 38486. Immunoblottlng studies revealed the selective translocatlon of PKC-αfrom the cytosollc fraction to the paniculate fraction upon glucocortlcold treatment. These results suggest that glucocorticold-lnduced apoptosis in immature thymocytes involves glucocorticold receptor-mediated and selective activation of PKC-αthrough de novo synthesis of macromolecules.

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