INVOLVEMENT OF ORNITHINE DECARBOXYLASE AND POLYAMINES IN GLUCOCORTICOID-INDUCED APOPTOSIS OF RAT THYMOCYTES

被引:0
|
作者
DESIDERIO, MA
GRASSILLI, E
BELLESIA, E
SALOMONI, P
FRANCESCHI, C
机构
[1] UNIV MILAN,CTR RES CELL PATHOL,CNR,I-20133 MILAN,ITALY
[2] UNIV MODENA,DEPT BIOMED SCI,GEN PATHOL SECT,I-41100 MODENA,ITALY
来源
CELL GROWTH & DIFFERENTIATION | 1995年 / 6卷 / 05期
关键词
D O I
暂无
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine metabolism, has been shown to be required for entry into and progression through the cell cycle. However, the role of ODC and polyamines in apoptosis remains to be determined. We have examined ODC expression and polyamine levels in thymocytes activated to undergo apoptosis by dexamethasone treatment. We have demonstrated a rapid and reversible induction of ODC (mRNA and activity), as previously reported for the mRNA expression of other ''early'' genes, c-fos, c-jun, and c-myc, in the same experimental model. Surprisingly, polyamine levels diminished progressively starting at 2-4 h after dexamethasone treatment, and spermine was depleted at 8-12 h. This seemed to be relevant since increasing the intracellular polyamine levels by exogenous spermine administration prevented the DNA ''laddering'' (2-4 h) and the DNA loss from the nucleus (8-18 h) due to dexamethasone treatment. Moreover, the activities of spermidine/spermine N-1-acetyltransferase, which controls the cytosolic polyamine interconversion pathway, and of spermidine N-8-acetyltransferase, which regulates the nuclear pool and functions of polyamines, were measured in apoptotic cells. Spermidine/spermine N-1-acetyltransferase activity progressively increased and might be responsible for spermidine and spermine excretion as acetyl derivatives. In contrast, spermidine N-8-acetyltransferase activity remained unchanged. A completely different scenario was observed in proliferating concanavalin A-treated thymocytes, studied for comparison. In this case, polyamine levels increased, remaining at high values until 12 h. This is likely a consequence of the rapid and prolonged induction of ODC (mRNA and activity), accompanied by that of spermidine/spermine N-1-acetyltransferase (mRNA and activity). Spermidine N-8-acetyltransferase activity peaked biphasically, indicating its possible involvement in the enhanced gene expression necessary for cell proliferation. Thus, the decrease in intracellular polyamine levels may represent a signal to thymocytes for progression into the apoptotic program.
引用
收藏
页码:505 / 513
页数:9
相关论文
共 50 条
  • [1] Involvement of Bax protein in the prevention of glucocorticoid-induced thymocytes apoptosis by melatonin
    Hoijman, E
    Viegas, LR
    Sarmiento, MIK
    Rosenstein, RE
    Pecci, A
    [J]. ENDOCRINOLOGY, 2004, 145 (01) : 418 - 425
  • [2] INVOLVEMENT OF PROTEIN KINASE-C-EPSILON IN GLUCOCORTICOID-INDUCED APOPTOSIS IN THYMOCYTES
    IWATA, M
    ISEKI, R
    SATO, K
    TOZAWA, Y
    OHOKA, Y
    [J]. INTERNATIONAL IMMUNOLOGY, 1994, 6 (03) : 431 - 438
  • [3] GLUCOCORTICOID-INDUCED ENDONUCLEASE ACTIVITY IN RAT THYMOCYTES
    HUGHES, JP
    COMPTON, MM
    CIDLOWSKI, JA
    [J]. JOURNAL OF DENTAL RESEARCH, 1986, 65 : 288 - 288
  • [4] Delineation of the signaling pathways involved in glucocorticoid-induced and spontaneous apoptosis of rat thymocytes
    Mann, CL
    Hughes, FM
    Cidlowski, JA
    [J]. ENDOCRINOLOGY, 2000, 141 (02) : 528 - 538
  • [5] Signaling pathways involved in glucocorticoid-induced apoptosis of thymocytes
    Lépine, S
    Sulpice, JC
    Giraud, F
    [J]. CRITICAL REVIEWS IN IMMUNOLOGY, 2005, 25 (04) : 263 - 288
  • [6] INVOLVEMENT OF PROTEIN-KINASE C-EPSILON IN GLUCOCORTICOID-INDUCED APOPTOSIS IN MURINE THYMOCYTES
    IWATA, M
    ISEKI, R
    TOZAWA, Y
    SATO, K
    ZHAO, Y
    OHOKA, Y
    [J]. FASEB JOURNAL, 1994, 8 (05): : A786 - A786
  • [7] INVOLVEMENT OF CALCIUM-INDEPENDENT LIPID-STIMULATED KINASE IN GLUCOCORTICOID-INDUCED APOPTOSIS IN THYMOCYTES
    IWATA, M
    ISEKI, R
    TOZAWA, Y
    SATO, K
    [J]. JOURNAL OF IMMUNOLOGY, 1993, 150 (08): : A31 - A31
  • [8] ORNITHINE DECARBOXYLASE AND ORNITHINE DECARBOXYLASE-INHIBITING ACTIVITY IN RAT THYMOCYTES
    STEFANELLI, C
    ROSSONI, C
    FERRARI, F
    FLAMIGNI, F
    CALDARERA, CM
    [J]. CELL BIOCHEMISTRY AND FUNCTION, 1992, 10 (04) : 243 - 250
  • [9] In vivo resistance to glucocorticoid-induced apoptosis in rat thymocytes with normal steroid receptor function in vitro
    Oldenburg, NBE
    EvansStorms, RB
    Cidlowski, JA
    [J]. ENDOCRINOLOGY, 1997, 138 (02) : 810 - 818
  • [10] STUDIES OF THE MECHANISM OF GLUCOCORTICOID-INDUCED PYKNOSIS IN ISOLATED RAT THYMOCYTES
    THOMAS, N
    EDWARDS, JL
    BELL, PA
    [J]. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1983, 18 (05): : 519 - 524