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
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.