title: Involvement of protein kinase C-epsilon in glucocorticoid-induced apoptosis in thymocytes.
abstract: Apoptosis is induced in immature thymocytes by physiological peak levels of glucocorticoid hormones, especially in murine and rat cells. Endogenous glucocorticoids may have some role in thymic selection. Glucocorticoid-induced 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 Ca(2+)-dependent (PKC-alpha, -beta I, -beta II, and -gamma) and Ca(2+)-independent (PKC-delta, -epsilon, -eta (L), -theta, -zeta, and -lambda) isozymes. In the present study, we analyzed the role of PKC in glucocorticoid-induced apoptosis in murine thymocytes and found that glucocorticoid selectively induces an increase in Ca(2+)-independent PKC activity in the particulate fraction of immature thymocytes but not in that of mature T cells. The increase as well as the apoptosis was inhibited by actinomycin D, cycloheximide, or the glucocorticoid receptor antagonist, RU 38486. Immunoblotting studies revealed the selective translocation of PKC-epsilon from the cytosolic fraction to the particulate fraction upon glucocorticoid treatment. These results suggest that glucocorticoid-induced apoptosis in immature thymocytes involves glucocorticoid receptor-mediated and selective activation of PKC-epsilon through de novo synthesis of macromolecules.
authors.affiliation: Laboratory of Cellular Immunology, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Iwata
authors.forename: R
authors.initials: R
authors.lastname: Iseki
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Tozawa
authors.forename: Y
authors.initials: Y
authors.lastname: Ohoka
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000502:physiology; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015151:Immunoblotting; D007527:Isoenzymes / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology* / Q000201:enzymology
chemical_list: D005938:Glucocorticoids; D007527:Isoenzymes; D011493:Protein Kinase C