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Different roles of spermine in glucocorticoid- and Fas-induced apoptosis

Author

Summary, in English

Two experimental systems representative of the mitochondrial and death receptor apoptotic pathways are the dexamethasone-induced programmed cell death in mouse thymocytes and the antibody-mediated cross-ligation of the Fas receptor in the human leukemic T-cell line Jurkat, respectively. In both cell systems, caspase-9, -8, and -3 were activated upon induction of apoptosis and a sub-G(1) peak appeared as a sign of ongoing DNA fragmentation. Addition of 1 mM spermine together with dexamethasone inhibited caspase activation and the appearance of the sub-G(1) peak in mouse thymocytes. In contrast, Fas-induced cell death was totally unaffected by spermine addition. Spermine addition significantly elevated the spermine concentration in both thymocytes and Jurkat cells. Thus, spermine per se did not inhibit the caspases but rather their activation. The fact that spermine inhibited caspase activation only in the thymocytes implies that spermine inhibited dexamethasone-induced apoptosis upstream of caspase-9 activation.

Publishing year

2001

Language

English

Pages

333-341

Publication/Series

Experimental Cell Research

Volume

266

Issue

2

Document type

Journal article

Publisher

Academic Press

Topic

  • Cancer and Oncology

Keywords

  • glucocorticoid
  • apoptosis
  • Fas death receptor
  • thymocytes
  • Jurkat cells
  • sub-G1 peak
  • cell cycle phase distribution
  • polyamines
  • caspases
  • flow cytometry

Status

Published

ISBN/ISSN/Other

  • ISSN: 1090-2422