| First Author | Asada A | Year | 1998 |
| Journal | J Biol Chem | Volume | 273 |
| Issue | 43 | Pages | 28392-8 |
| PubMed ID | 9774466 | Mgi Jnum | J:115241 |
| Mgi Id | MGI:3691172 | Doi | 10.1074/jbc.273.43.28392 |
| Citation | Asada A, et al. (1998) Induction of thymocyte apoptosis by Ca2+-independent protein kinase C (nPKC) activation and its regulation by calcineurin activation. J Biol Chem 273(43):28392-8 |
| abstractText | Glucocorticoids appear to participate in apoptosis of unselected CD4(+)CD8(+) thymocytes. Activation of Ca2+-independent novel protein kinase C (nPKC) precedes glucocorticoid-induced thymocyte apoptosis, while proper levels of Ca2+-dependent protein kinase C (cPKC) and calcineurin activities contribute to rescue thymocytes. To clarify the role of nPKC in thymocyte apoptosis, murine thymocytes were stimulated with the diterpene diester, ingenol 3, 20-dibenzoate (IDB). IDB induced selective translocation of nPKC-delta, -epsilon, and -theta and PKC-mu from the cytosolic fraction to the particulate fraction and induced morphologically typical apoptosis through de novo synthesis of macromolecules. The apoptosis was also induced by thymeleatoxin, a diterpene ester, at relatively high concentrations that induced translocation of cPKC, nPKC-theta, and PKC-mu. The IDB- or thymeleatoxin-induced death was inhibited by non-isoform-selective PKC inhibitors, but not by their structural analogs with weak PKC-inhibitory activity or the selective inhibitor of cPKC and PKC-mu, Go 6976. The death was also inhibited by calcium ionophore ionomycin at concentrations within a narrow range. The range corresponded to the concentration range that contributes to the inhibition of glucocorticoid-induced apoptosis. The antiapoptotic effect was canceled by the immunosuppressant FK506 but not by rapamycin. These results indicate that activation of nPKC, especially nPKC-theta, induces apoptosis in thymocytes and that calcineurin activation regulates the apoptosis. |
