Involvement of protein kinase C-epsilon in glucocorticoid-induced apoptosis in thymocytes.
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.
Iwata
M
M
Laboratory of Cellular Immunology, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Iseki
R
R
Sato
K
K
Tozawa
Y
Y
Ohoka
Y
Y
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
D005938:Glucocorticoids; D007527:Isoenzymes; D011493:Protein Kinase C