ACTIVATION OF INTERLEUKIN-1-BETA-CONVERTING ENZYME BY NIGERICIN IS INDEPENDENT OF APOPTOSIS

Citation
N. Watanabe et al., ACTIVATION OF INTERLEUKIN-1-BETA-CONVERTING ENZYME BY NIGERICIN IS INDEPENDENT OF APOPTOSIS, Cytokine (Philadelphia, Pa. Print), 10(9), 1998, pp. 645-653
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell Biology",Biology,Immunology
ISSN journal
1043-4666
Volume
10
Issue
9
Year of publication
1998
Pages
645 - 653
Database
ISI
SICI code
1043-4666(1998)10:9<645:AOIEBN>2.0.ZU;2-O
Abstract
Interleukin-1 beta-converting enzyme (ICE) is believed to be one of th e key proteases involved in apoptosis. Since the precursor form of int erleukin-1 beta (pre-IL-1 beta) is one of the well-known substrates fo r ICE, and a potassium/proton ionophore, nigericin, enhances IL-1 beta processing, the authors hypothesized that nigericin induces apoptosis through the activation of ICE. In a lipopolysaccharide (LPS)-stimulat ed and nigericin-treated human monocytic cell line, THP-1, apoptosis w as induced, as assessed as to a decrease in cell size, chromatin conde nsation, exposure of phosphatidylserine and DNA fragmentation. Under e xactly the same conditions, nigericin also induced IL-1 beta processin g in these cells, which was significantly inhibited by an ICE inhibito r, acetyl-Tyr-Val-Ala-Asp-CHO. On the contrary, treatment with this in hibitor at the same concentration did not inhibit nigericin-induced ap optosis, assessed as to the decrease in cell size, chromatin condensat ion and DNA fragmentation. Although apoptosis induced by nigericin was also observed for LPS-stimulated human peripheral blood mononuclear c ells and a mouse T lymphoma cell line, EL-4, the ICE inhibitor did not inhibit the apoptosis in the cells. These results suggest that activa ted ICE is not involved in the apoptosis induced by nigericin, Since a popain activity was not augmented under the same conditions, neither I CE nor apopain may play any role in the nigericin-induced apoptosis. ( C) 1998 Academic Press.