PMID: 11902113Mar 21, 2002Paper

Essential role of caspase-11 in activation-induced cell death of rat astrocytes

Journal of Neurochemistry
Kyoungho SukHocheol Kim

Abstract

We have previously shown that rat astrocytes undergo apoptosis upon inflammatory activation. Nitric oxide (NO) produced by activated astrocytes was the major cytotoxic mediator in this type of autoregulatory apoptosis. However, an inhibitor of nitric oxide synthase did not completely block the apoptosis of activated astrocytes, suggesting the presence of other apoptotic pathways. Here, we present evidence that caspase-11 is an essential molecule in NO-independent apoptotic pathway of activated astrocytes. Inflammatory activation (lipopolysaccharide, interferon-gamma, and tumor necrosis factor-alpha treatment) of rat astrocyte cultures and C6 glioma cells led to the induction of caspase-11 followed by activation of caspases-11, -1, and -3. In contrast, NO donors induced activation of caspase-3 only. Inactivation of caspase-11 by the transfection of dominant negative mutant or treatment with the caspase inhibitors rendered the astrocytes partially resistant to the apoptosis following inflammatory activation, but not NO donor exposure. These results indicate that inflammatory stimuli not only induce the production of cytotoxic NO, but also initiate NO-independent apoptotic pathway through the induction of caspase-11 expression.

Citations

Jun 28, 2003·Brain Research. Molecular Brain Research·Nam-Gon KimKyoungho Suk
Aug 17, 2004·DNA and Cell Biology·Shin-Jung KangStephen T Sonis
Apr 11, 2009·Journal of Neuroscience Research·Guo Nan YinKyoungho Suk
Aug 9, 2006·Journal of Neurochemistry·Jiyeon OckKyoungho Suk
Oct 29, 2009·Journal of Neurochemistry·Long Tai ZhengKyoungho Suk
Apr 6, 2004·Progress in Neurobiology·Kazuhiro TakumaToshio Matsuda
Sep 6, 2013·Nature·Vijay A K Rathinam, Katherine A Fitzgerald
Apr 25, 2006·The Journal of Gene Medicine·Béla DénesIstván Fodor
Dec 2, 2006·Journal of Neuroscience Research·Guglielmo R D VillaniPaola Di Natale
Apr 23, 2005·Glia·Rona G Giffard, Raymond A Swanson
Feb 28, 2003·The Journal of Pharmacology and Experimental Therapeutics·Kyoungho SukWan Sung Choi
Feb 19, 2013·Expert Review of Proteomics·Mithilesh Kumar Jha, Kyoungho Suk
May 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dae Young JungKyoungho Suk
Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heasuk LeeKyoungho Suk

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