PMID: 9420624Jan 8, 1998Paper

Involvement of ICE (Caspase) family in gamma-radiation-induced apoptosis of normal B lymphocytes

Scandinavian Journal of Immunology
E HallanJ Lømo

Abstract

Normal lymphocytes are highly sensitive to the damaging effects of ionizing radiation, and undergo cell death by apoptosis. We have investigated the possible involvement of the Interleukin-1 beta-converting enzyme (ICE) (Caspase) protease family, which appears to play an important role as intracellular mediator of apoptosis. Resting B lymphocytes isolated from human peripheral blood were irradiated (6 Gy) and cultured for 24 h, resulting in 25 +/- 5.1% apoptotic cells, as measured by the TUNEL assay (mean +/- SD, n = 6). Addition of the ICE family inhibitor Z-VAD.fmk (50 microM) completely inhibited apoptosis (2.0 +/- 1.5% at 24 h). By using fluorogenic substrates containing the peptide recognition sequences DEVD and YVAD, the type of ICE family protease involved was examined more closely. A marked transient increase in DEVD-, and absent YVAD-cleavage activity indicated the involvement of a CPP32-like protease, not an ICE-like protease. Western blot analysis demonstrated that untreated B lymphocytes expressed the proform of the ICE family members CPP32 and ICH1L, but no detectable ICE. The induction of cell death by radiation was accompanied by the activation of CPP32 as shown by the cleavage of the proform to the active subuni...Continue Reading

Citations

Mar 30, 1999·Experimental Cell Research·B ZhivotovskyS Orrenius
Nov 1, 2008·Transplant Immunology·Jean-Paul Dehoux, Pierre Gianello
Mar 26, 2002·The Journal of Biological Chemistry·Peter E LonerganMarina A Lynch

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