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| Glucocorticoid-induced apoptosis and regulation of NF-kappa B activity in human leukemic T cells |
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| Author(s): Ramdas J, Harmon JM |
| Source: ENDOCRINOLOGY Volume: 139 Issue: 9 Pages: 3813-3821 Published: SEP 1998 |
| Times Cited: 41 References: 78 |
| Abstract: Glucocorticoid-induced apoptosis was investigated in glucocorticoid-sensitive 6TG1.1 and resistant ICR27TK.3 human leukemic T cells. Following glucocorticoid treatment of 6TGl.l cells, chromatin fragmentation was observed after a delay of 24 h. Fragmentation was not observed in ICR27TK.3 cells containing mutant glucocorticoid receptors (L753F) that are activation-deficient but retain the ability to repress AP-1 activity. Nor was fragmentation observed after treatment with RU38486, indicating that repression of AP-1 activity is not involved. As described in other systems, fragmentation required ongoing protein synthesis. However, inhibition of protein synthesis with cycloheximide anytime during the first 18 h of steroid treatment was as effective in blocking chromatin fragmentation as inhibition for the entire period, suggesting that synthesis of a component with a rapid turnover rate is required. Dexamethasone treatment completely blocked 12-O-tetradecanoylphorbol 13-acetate induction of nuclear factor-kappa B (NF-kappa B) activity and elicited an increase in the amount of immunoreactive I kappa B alpha in sensitive 6TG1.1 cells but not in resistant ICR27TK.3 cells. In addition, mild detergent treatment of cell extracts indicated that a substantial amount of cytoplasmic NF-kappa B is complexed with I kappa B alpha or some other inhibitory factor. These results suggest that induction of a labile inhibitory factor such as I kappa B alpha may contribute to glucocorticoid-induced apoptosis. |
| Document Type: Article |
| Language: English |
| Reprint Address: Harmon, JM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pharmacol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA |
Addresses:
1. Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA |
| Publisher: ENDOCRINE SOC, 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA |
| Subject Category: Endocrinology & Metabolism |
| IDS Number: 112NK |
| ISSN: 0013-7227 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |