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Carbon monoxide protects hepatocytes from TNF-alpha/Actinomycin D by inhibition of the caspase-8-mediated apoptotic pathway.

Abstract

We have previously shown that carbon monoxide (CO) (250 ppm) prevented tumor necrosis factor-alpha (TNFalpha)-induced apoptosis and activated the transcription factor NF-kappaB in hepatocytes both in vivo and in vitro. These studies were conducted to further determine the mechanisms by which CO suppresses apoptotic signaling in TNFalpha (10 ng/ml) and Actinomycin D (ActD, 200 ng/ml)-treated hepatocytes. Consistent with our previous findings, CO protected against TNFalpha/ActD-induced cell death, which is in part dependent on NF-kappaB activation. This was associated with a reduction in mitochondrial damage, a decrease in cytochrome c release, and an inhibition of translocation of Bcl proteins to mitochondria. In conjugation with inhibition of these mitochondrial events, CO also suppressed caspases-8 and -3 cleavage in response to TNFalpha/ActD. Inhibition of NF-kappaB activation resulted in diminished CO-induced cFLIP expression and increased caspase-8 cleavage from cells treated with TNFalpha/ActD. These data indicate that CO interferes with apoptotic signaling at a proximal step.

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  • Authors+Show Affiliations

    ,

    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

    , , ,

    Source

    MeSH

    Animals
    Apoptosis
    CASP8 and FADD-Like Apoptosis Regulating Protein
    Carbon Monoxide
    Caspase 8
    Caspase Inhibitors
    Cells, Cultured
    Dactinomycin
    Hepatocytes
    Inhibitor of Apoptosis Proteins
    Intracellular Signaling Peptides and Proteins
    Mice
    Mitochondria
    NF-kappa B
    Protein Transport
    Proto-Oncogene Proteins c-bcl-2
    Tumor Necrosis Factor-alpha
    Up-Regulation

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    16647044

    Citation

    Kim, Hoe Suk, et al. "Carbon Monoxide Protects Hepatocytes From TNF-alpha/Actinomycin D By Inhibition of the Caspase-8-mediated Apoptotic Pathway." Biochemical and Biophysical Research Communications, vol. 344, no. 4, 2006, pp. 1172-8.
    Kim HS, Loughran PA, Kim PK, et al. Carbon monoxide protects hepatocytes from TNF-alpha/Actinomycin D by inhibition of the caspase-8-mediated apoptotic pathway. Biochem Biophys Res Commun. 2006;344(4):1172-8.
    Kim, H. S., Loughran, P. A., Kim, P. K., Billiar, T. R., & Zuckerbraun, B. S. (2006). Carbon monoxide protects hepatocytes from TNF-alpha/Actinomycin D by inhibition of the caspase-8-mediated apoptotic pathway. Biochemical and Biophysical Research Communications, 344(4), pp. 1172-8.
    Kim HS, et al. Carbon Monoxide Protects Hepatocytes From TNF-alpha/Actinomycin D By Inhibition of the Caspase-8-mediated Apoptotic Pathway. Biochem Biophys Res Commun. 2006 Jun 16;344(4):1172-8. PubMed PMID: 16647044.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Carbon monoxide protects hepatocytes from TNF-alpha/Actinomycin D by inhibition of the caspase-8-mediated apoptotic pathway. AU - Kim,Hoe Suk, AU - Loughran,Patricia A, AU - Kim,Peter K, AU - Billiar,Timothy R, AU - Zuckerbraun,Brian S, Y1 - 2006/04/06/ PY - 2006/03/22/received PY - 2006/03/24/accepted PY - 2006/5/2/pubmed PY - 2006/7/20/medline PY - 2006/5/2/entrez SP - 1172 EP - 8 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 344 IS - 4 N2 - We have previously shown that carbon monoxide (CO) (250 ppm) prevented tumor necrosis factor-alpha (TNFalpha)-induced apoptosis and activated the transcription factor NF-kappaB in hepatocytes both in vivo and in vitro. These studies were conducted to further determine the mechanisms by which CO suppresses apoptotic signaling in TNFalpha (10 ng/ml) and Actinomycin D (ActD, 200 ng/ml)-treated hepatocytes. Consistent with our previous findings, CO protected against TNFalpha/ActD-induced cell death, which is in part dependent on NF-kappaB activation. This was associated with a reduction in mitochondrial damage, a decrease in cytochrome c release, and an inhibition of translocation of Bcl proteins to mitochondria. In conjugation with inhibition of these mitochondrial events, CO also suppressed caspases-8 and -3 cleavage in response to TNFalpha/ActD. Inhibition of NF-kappaB activation resulted in diminished CO-induced cFLIP expression and increased caspase-8 cleavage from cells treated with TNFalpha/ActD. These data indicate that CO interferes with apoptotic signaling at a proximal step. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/16647044/Carbon_monoxide_protects_hepatocytes_from_TNF_alpha/Actinomycin_D_by_inhibition_of_the_caspase_8_mediated_apoptotic_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(06)00713-3 DB - PRIME DP - Unbound Medicine ER -