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Article ; Online: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) deletion in myeloid cells augments cholestatic liver injury.

Krishnan, Anuradha / Ozturk, Nazli Begum / Cutshaw, Kaiyel A / Guicciardi, Maria Eugenia / Kitagataya, Takashi / Olson, Kirsta E / Pavelko, Kevin D / Sherman, William / Wixom, Alexander Q / Jalan-Sakrikar, Nidhi / Baez-Faria, Michelle / Gutierrez, Florencia / Gores, Gregory J

Scientific reports

2024 Volume 14, Issue 1, Page(s) 2145

Abstract: Ductular reactive (DR) cells exacerbate cholestatic liver injury and fibrosis. Herein, we posit that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) emanates from recruited macrophages and restrains DR cell expansion, thereby limiting ... ...

Abstract	Ductular reactive (DR) cells exacerbate cholestatic liver injury and fibrosis. Herein, we posit that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) emanates from recruited macrophages and restrains DR cell expansion, thereby limiting cholestatic liver injury. Wild type (WT), Trail
MeSH term(s)	Animals ; Mice ; Apoptosis/genetics ; Cholestasis/metabolism ; Fibrosis ; Ligands ; Liver/metabolism ; Macrophages/metabolism ; Mice, Inbred C57BL ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Ligands ; Tumor Necrosis Factor-alpha ; Tnfsf10 protein, mouse
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-52710-3
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Article ; Online: Cell stress gives a red light to the mitochondrial cell death pathway.

Guicciardi, M Eugenia / Gores, Gregory J

Science signaling

2008 Volume 1, Issue 7, Page(s) pe9

Abstract: Although the ultimate outcome of prolonged exposure of cells to stress is often death, the early response appears to be the activation of survival pathways that are likely to give the cell an opportunity to repair low-level damage. How these stress- ... ...

Abstract	Although the ultimate outcome of prolonged exposure of cells to stress is often death, the early response appears to be the activation of survival pathways that are likely to give the cell an opportunity to repair low-level damage. How these stress-initiated survival pathways influence B cell lymphoma/leukemia 2 (Bcl-2) proteins, the core cell death machinery, has remained unclear; however, two papers now provide insight into stress-mediated survival mechanisms. The liver is unusually resistant to p53-mediated apoptosis. It appears that p53-mediated induction of the gene that encodes insulin-like growth factor-binding protein-1 (IGFBP1) attenuates the cell death response in hepatocytes by preventing the formation of a complex between p53 and the proapoptotic protein BAK. This is especially interesting as IGFBP1 is not a member of the Bcl-2 family, yet it inhibited BAK. In three unrelated cell lines, another regulatory interaction that influences cell survival occurs at the mitochondria. In this case, protein phosphatase 1gamma (PP1gamma) regulated the phosphorylation status of the Bcl-2/Bcl-X(L)-associated death promoter (BAD). The prefoldin family member URI is normally phosphorylated by S6 kinase 1, which liberates PP1gamma from a URI-PP1gamma complex. However, the withdrawal of growth factors or nutrients stabilizes this complex, which renders PP1gamma inactive. The net response of this stress stimulus is an increased abundance of phosphorylated BAD, which raises the threshold required to trigger cell death. These two studies have identified new players and mechanisms that integrate stress responses and cell death.
MeSH term(s)	Animals ; Apoptosis ; Cell Death ; Cell Line ; Hepatocytes/cytology ; Hepatocytes/metabolism ; Humans ; Insulin-Like Growth Factor Binding Protein 1/metabolism ; Mitochondria/metabolism ; Mitochondria, Liver/metabolism ; Protein Phosphatase 1/physiology ; Proto-Oncogene Proteins c-bcl-2/physiology ; Ribosomal Protein S6 Kinases/physiology ; Signal Transduction ; Tumor Suppressor Protein p53/physiology ; bcl-Associated Death Protein/physiology
Chemical Substances	IGFBP1 protein, human ; Insulin-Like Growth Factor Binding Protein 1 ; Proto-Oncogene Proteins c-bcl-2 ; Tumor Suppressor Protein p53 ; bcl-Associated Death Protein ; Ribosomal Protein S6 Kinases (EC 2.7.11.1) ; Protein Phosphatase 1 (EC 3.1.3.16)
Language	English
Publishing date	2008-02-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2417226-1
ISSN	1937-9145 ; 1945-0877
ISSN (online)	1937-9145
ISSN	1945-0877
DOI	10.1126/stke.17pe9
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Article: Cheating death in the liver.

Guicciardi, M Eugenia / Gores, Gregory J

Nature medicine

2004 Volume 10, Issue 6, Page(s) 587–588

MeSH term(s)	Animals ; Apoptosis/drug effects ; Disease Models, Animal ; Fas Ligand Protein ; Hepatitis/drug therapy ; Hepatitis/metabolism ; Hepatitis/pathology ; Humans ; Liver/drug effects ; Liver/pathology ; Liver/physiology ; Membrane Glycoproteins/metabolism ; Mice ; Signal Transduction/physiology ; Suramin/pharmacology ; Suramin/therapeutic use ; Trypanocidal Agents/pharmacology ; Trypanocidal Agents/therapeutic use ; fas Receptor/metabolism
Chemical Substances	FASLG protein, human ; Fas Ligand Protein ; Fasl protein, mouse ; Membrane Glycoproteins ; Trypanocidal Agents ; fas Receptor ; Suramin (6032D45BEM)
Language	English
Publishing date	2004-06
Publishing country	United States
Document type	News ; Comment
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/nm0604-587
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Article: Targeted use of siRNA in animal models of hepatic damage: an innovative therapy for acute liver failure.

Guicciardi, M Eugenia / Gores, Gregory J

Journal of hepatology

2003 Volume 39, Issue 5, Page(s) 883–885

MeSH term(s)	Acute Disease ; Animals ; Gene Silencing ; Gene Targeting ; Liver Failure/genetics ; Liver Failure/physiopathology ; Liver Failure/therapy ; RNA, Small Interfering ; Receptors, Tumor Necrosis Factor/genetics ; Receptors, Tumor Necrosis Factor/metabolism
Chemical Substances	RNA, Small Interfering ; Receptors, Tumor Necrosis Factor
Language	English
Publishing date	2003-10-16
Publishing country	Netherlands
Document type	Comment ; Journal Article
ZDB-ID	605953-3
ISSN	1600-0641 ; 0168-8278
ISSN (online)	1600-0641
ISSN	0168-8278
DOI	10.1016/s0168-8278(03)00429-x
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Article: Ursodeoxycholic acid cytoprotection: dancing with death receptors and survival pathways.

Guicciardi, M Eugenia / Gores, Gregory J

Hepatology (Baltimore, Md.)

2002 Volume 35, Issue 4, Page(s) 971–973

MeSH term(s)	Animals ; Apoptosis/drug effects ; Cell Survival/physiology ; Cholagogues and Choleretics/pharmacology ; Cytoprotection/physiology ; Humans ; Receptors, Tumor Necrosis Factor/physiology ; Ursodeoxycholic Acid/pharmacology
Chemical Substances	Cholagogues and Choleretics ; Receptors, Tumor Necrosis Factor ; Ursodeoxycholic Acid (724L30Y2QR)
Language	English
Publishing date	2002-04
Publishing country	United States
Document type	Comment ; Editorial ; Review
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1053/jhep.2002.32931
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Article: AIP1: a new player in TNF signaling.

Guicciardi, M Eugenia / Gores, Gregory J

The Journal of clinical investigation

2003 Volume 111, Issue 12, Page(s) 1813–1815

Abstract: Apoptosis signal-regulating kinase 1 (ASK1) is an upstream activator of JNK and p38 MAPK signaling cascades. Evidence now shows that the ASK1-interacting protein, AIP1, plays an important role in TNF-alpha-induced ASK1 activation by facilitating ... ...

Abstract	Apoptosis signal-regulating kinase 1 (ASK1) is an upstream activator of JNK and p38 MAPK signaling cascades. Evidence now shows that the ASK1-interacting protein, AIP1, plays an important role in TNF-alpha-induced ASK1 activation by facilitating dissociation from its inhibitor.
MeSH term(s)	Antigens, CD/physiology ; Apoptosis/physiology ; Enzyme Activation ; Enzyme Inhibitors/metabolism ; Humans ; MAP Kinase Kinase Kinase 5 ; MAP Kinase Kinase Kinases/antagonists & inhibitors ; MAP Kinase Kinase Kinases/physiology ; MAP Kinase Signaling System ; Receptors, Tumor Necrosis Factor/physiology ; Receptors, Tumor Necrosis Factor, Type I ; Receptors, Tumor Necrosis Factor, Type II ; Tumor Necrosis Factor-alpha/physiology ; ras GTPase-Activating Proteins/physiology
Chemical Substances	Antigens, CD ; Enzyme Inhibitors ; Receptors, Tumor Necrosis Factor ; Receptors, Tumor Necrosis Factor, Type I ; Receptors, Tumor Necrosis Factor, Type II ; Tumor Necrosis Factor-alpha ; ras GTPase-Activating Proteins ; MAP Kinase Kinase Kinase 5 (EC 2.7.11.25) ; MAP Kinase Kinase Kinases (EC 2.7.11.25) ; MAP3K5 protein, human (EC 2.7.11.25)
Language	English
Publishing date	2003-06
Publishing country	United States
Document type	Comment ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI18911
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Article: TNF-alpha-mediated lysosomal permeabilization is FAN and caspase 8/Bid dependent.

Werneburg, Nate / Guicciardi, M Eugenia / Yin, Xiao-Ming / Gores, Gregory J

American journal of physiology. Gastrointestinal and liver physiology

2004 Volume 287, Issue 2, Page(s) G436–43

Abstract: TNF-alpha cytotoxic signaling involves lysosomal permeabilization with release of the lysosomal protease cathepsin B (ctsb) into the cytosol. However, the mechanisms mediating lysosomal breakdown remain unclear. Because caspase-8 and factor associated ... ...

Abstract	TNF-alpha cytotoxic signaling involves lysosomal permeabilization with release of the lysosomal protease cathepsin B (ctsb) into the cytosol. However, the mechanisms mediating lysosomal breakdown remain unclear. Because caspase-8 and factor associated with neutral sphingomyelinase activation (FAN) have been implicated as proximal mediators of TNF-alpha-associated apoptosis, their role in lysosomal permeabilization was examined. Cellular distribution of ctsb-green fluorescent protein (ctsb-GFP) in a rat hepatoma cell line was imaged by confocal microscopy. ctsb-GFP fluorescence was punctate under basal conditions but became diffuse after treatment with TNF-alpha/actinomycin D. This cellular redistribution of ctsb-GFP was blocked by transfection with a vector expressing a dominant-negative Fas-associated protein with death domain (DeltaFADD), cytokine response modifier A, or a pharmacological caspase-8 inhibitor, IETD-fmk. Consistent with the concept that caspase 8-mediated apoptosis is also Bid-dependent in hepatocytes, ctsb-GFP release from lysosomes was reduced in hepatocytes from Bid(-/-) mice. Interestingly, transfection with a vector expressing a dominant-negative FAN (DeltaFAN) also blocked ctsb-GFP release and caspase-8 activation. Paradigms that inhibited ctsb-GFP release from lysosomes also reduced apoptosis as assessed by morphology and biochemical criteria. In conclusion, these studies suggest FAN is upstream of caspase-8/Bid in a signaling cascade culminating in lysosomal permeabilization.
MeSH term(s)	Adaptor Proteins, Signal Transducing ; Animals ; Apoptosis/physiology ; BH3 Interacting Domain Death Agonist Protein ; Carrier Proteins/genetics ; Carrier Proteins/physiology ; Caspase 8 ; Caspases/metabolism ; Caspases/physiology ; Cathepsin B/metabolism ; Cells, Cultured ; Dactinomycin/pharmacology ; Enzyme Activation/drug effects ; Fas-Associated Death Domain Protein ; Green Fluorescent Proteins ; Intracellular Signaling Peptides and Proteins ; Luminescent Proteins/genetics ; Lysosomes/metabolism ; Mice ; Mice, Knockout ; Permeability/drug effects ; Proteins/physiology ; Rats ; Recombinant Fusion Proteins/pharmacology ; Tumor Necrosis Factor-alpha/pharmacology ; Tumor Necrosis Factor-alpha/physiology
Chemical Substances	Adaptor Proteins, Signal Transducing ; BH3 Interacting Domain Death Agonist Protein ; Bid protein, mouse ; Bid protein, rat ; Carrier Proteins ; Fadd protein, mouse ; Fadd protein, rat ; Fas-Associated Death Domain Protein ; Intracellular Signaling Peptides and Proteins ; Luminescent Proteins ; Nsmaf protein, mouse ; Nsmaf protein, rat ; Proteins ; Recombinant Fusion Proteins ; Tumor Necrosis Factor-alpha ; Green Fluorescent Proteins (147336-22-9) ; Dactinomycin (1CC1JFE158) ; Casp8 protein, mouse (EC 3.4.22.-) ; Casp8 protein, rat (EC 3.4.22.-) ; Caspase 8 (EC 3.4.22.-) ; Caspases (EC 3.4.22.-) ; Cathepsin B (EC 3.4.22.1)
Language	English
Publishing date	2004-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	603840-2
ISSN	1522-1547 ; 0193-1857
ISSN (online)	1522-1547
ISSN	0193-1857
DOI	10.1152/ajpgi.00019.2004
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Article: Tumor necrosis factor-related apoptosis-inducing ligand activates a lysosomal pathway of apoptosis that is regulated by Bcl-2 proteins.

Werneburg, Nathan W / Guicciardi, M Eugenia / Bronk, Steve F / Kaufmann, Scott H / Gores, Gregory J

The Journal of biological chemistry

2007 Volume 282, Issue 39, Page(s) 28960–28970

Abstract: The present studies were performed to determine whether lysosomal permeabilization contributes to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) cytotoxicity and to reconcile a role for lysosomes with prior observations that Bcl-2 family ...

Abstract	The present studies were performed to determine whether lysosomal permeabilization contributes to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) cytotoxicity and to reconcile a role for lysosomes with prior observations that Bcl-2 family members regulate TRAIL-induced apoptosis. In KMCH cholangiocarcinoma cells stably expressing Mcl-1 small interference RNA (siRNA), treatment with TRAIL induced a redistribution of the cathepsin B from lysosomes to the cytosol. Pharmacological and small hairpin RNA-targeted inhibition of cathepsin B attenuated TRAIL-mediated apoptosis as assessed by morphological, biochemical, and clonogenic assays. Neither Bid siRNA nor Bak siRNA prevented cathepsin B release. In contrast, treatment of the cells with Bim siRNA or the JNK inhibitor SP600125 attenuated lysosomal permeabilization and cell death. Moreover, Bim and active Bax co-localized to lysosomes in TRAIL-treated cells in a JNK-dependent manner, and Bax siRNA reduced TRAIL-induced lysosomal permeabilization and cell death. Finally, BH3 domain peptides permeabilized isolated lysosomes in the presence of Bax. Collectively, these data suggest that TRAIL can trigger an apoptotic pathway that involves JNK-dependent activation of Bim, which in turn induces Bax-mediated permeabilization of lysosomes.
MeSH term(s)	Anthracenes/pharmacology ; Apoptosis/drug effects ; Apoptosis Regulatory Proteins/metabolism ; Bcl-2-Like Protein 11 ; Cathepsin B/antagonists & inhibitors ; Cathepsin B/metabolism ; Cell Death/drug effects ; Cell Line, Tumor ; Cell Membrane Permeability/drug effects ; Humans ; Lysosomes/metabolism ; MAP Kinase Kinase 4/antagonists & inhibitors ; MAP Kinase Kinase 4/metabolism ; Membrane Proteins/metabolism ; Myeloid Cell Leukemia Sequence 1 Protein ; Neoplasm Proteins/metabolism ; Peptides/metabolism ; Peptides/pharmacology ; Protein Structure, Tertiary ; Protein Transport/drug effects ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; RNA, Small Interfering/pharmacology ; TNF-Related Apoptosis-Inducing Ligand/metabolism ; TNF-Related Apoptosis-Inducing Ligand/pharmacology ; bcl-2 Homologous Antagonist-Killer Protein/metabolism ; bcl-2-Associated X Protein/metabolism
Chemical Substances	Anthracenes ; Apoptosis Regulatory Proteins ; BAK1 protein, human ; BAX protein, human ; BCL2L11 protein, human ; Bcl-2-Like Protein 11 ; Membrane Proteins ; Myeloid Cell Leukemia Sequence 1 Protein ; Neoplasm Proteins ; Peptides ; Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-bcl-2 ; RNA, Small Interfering ; TNF-Related Apoptosis-Inducing Ligand ; TNFSF10 protein, human ; bcl-2 Homologous Antagonist-Killer Protein ; bcl-2-Associated X Protein ; pyrazolanthrone (1TW30Y2766) ; MAP Kinase Kinase 4 (EC 2.7.12.2) ; Cathepsin B (EC 3.4.22.1)
Language	English
Publishing date	2007-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M705671200
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Article: Tumor necrosis factor-alpha-associated lysosomal permeabilization is cathepsin B dependent.

Werneburg, Nathan W / Guicciardi, M Eugenia / Bronk, Steven F / Gores, Gregory J

American journal of physiology. Gastrointestinal and liver physiology

2002 Volume 283, Issue 4, Page(s) G947–56

Abstract: Cathepsin B (Cat B) is released from lysososomes during tumor necrosis factor-alpha (TNF-alpha) cytotoxic signaling in hepatocytes and contributes to cell death. Sphingosine has recently been implicated in lysosomal permeabilization and is increased in ... ...

Abstract	Cathepsin B (Cat B) is released from lysososomes during tumor necrosis factor-alpha (TNF-alpha) cytotoxic signaling in hepatocytes and contributes to cell death. Sphingosine has recently been implicated in lysosomal permeabilization and is increased in the liver by TNF-alpha. Thus the aims of this study were to examine the mechanisms involved in TNF-alpha-associated lysosomal permeabilization, especially the role of sphingosine. Confocal microscopy demonstrated Cat B-green fluorescent protein and LysoTracker Red were both released from lysosomes after treatment of McNtcp.24 cells with TNF-alpha/actinomycin D, a finding compatible with lysosomal destabilization. In contrast, endosomes labeled with Texas Red dextran remained intact, suggesting lysosomes were specifically targeted for permeabilization. LysoTracker Red was released from lysosomes in hepatocytes treated with TNF-alpha or sphingosine in Cat B(+/+) but not Cat B(-/-) hepatocytes, as assessed by a fluorescence-based assay. With the use of a calcein release assay in isolated lysosomes, sphingosine permeabilized liver lysosomes isolated from Cat B(+/+) but not Cat B(-/-) liver. C(6) ceramide did not permeabilize lysosomes. In conclusion, these data implicate a sphingosine-Cat B interaction inducing lysosomal destabilization during TNF-alpha cytotoxic signaling.
MeSH term(s)	Animals ; Antigens, CD/genetics ; Apoptosis ; Cathepsin B/genetics ; Cathepsin B/physiology ; Cell Membrane Permeability ; Cells, Cultured ; Dactinomycin/pharmacology ; Fluorescent Dyes ; Green Fluorescent Proteins ; Hepatocytes/metabolism ; Hepatocytes/ultrastructure ; Liver Neoplasms, Experimental ; Luminescent Proteins/genetics ; Lysosomal Membrane Proteins ; Lysosomes/metabolism ; Membrane Glycoproteins/genetics ; Mice ; Mice, Knockout ; Microscopy, Confocal ; Microscopy, Electron ; Rats ; Recombinant Fusion Proteins/metabolism ; Sphingosine/pharmacology ; Transfection ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/metabolism ; Tumor Necrosis Factor-alpha/pharmacology
Chemical Substances	Antigens, CD ; Fluorescent Dyes ; Luminescent Proteins ; Lysosomal Membrane Proteins ; Membrane Glycoproteins ; Recombinant Fusion Proteins ; Tumor Necrosis Factor-alpha ; Green Fluorescent Proteins (147336-22-9) ; Dactinomycin (1CC1JFE158) ; Cathepsin B (EC 3.4.22.1) ; Sphingosine (NGZ37HRE42)
Language	English
Publishing date	2002-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	603840-2
ISSN	1522-1547 ; 0193-1857
ISSN (online)	1522-1547
ISSN	0193-1857
DOI	10.1152/ajpgi.00151.2002
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Article: Bid is upstream of lysosome-mediated caspase 2 activation in tumor necrosis factor alpha-induced hepatocyte apoptosis.

Guicciardi, M Eugenia / Bronk, Steven F / Werneburg, Nathan W / Yin, Xiao-Ming / Gores, Gregory J

Gastroenterology

2005 Volume 129, Issue 1, Page(s) 269–284

Abstract: Background & aims: During tumor necrosis factor alpha-mediated hepatocyte cytotoxicity, cathepsin B is released from lysosomes and contributes to apoptosis by indirectly promoting mitochondrial dysfunction. How this lysosomal pathway mediates ... ...

Abstract	Background & aims: During tumor necrosis factor alpha-mediated hepatocyte cytotoxicity, cathepsin B is released from lysosomes and contributes to apoptosis by indirectly promoting mitochondrial dysfunction. How this lysosomal pathway mediates mitochondrial dysfunction is unclear. Because Bcl-2 family proteins and caspase 2 have been implicated in proximal apoptosis-signaling pathways, we examined the role of these proteins in tumor necrosis factor alpha-induced lysosomal permeabilization and cathepsin B-mediated mitochondrial dysfunction. Methods: Studies were performed in primary hepatocytes from wild-type cathepsin B knockout, Bid knockout, and caspase 2 knockout mice and in the rat hepatoma cell line McArdle7777 by using tumor necrosis factor alpha/actinomycin D. Results: Studies in wild-type and Bid knockout hepatocytes showed that tumor necrosis factor alpha-mediated lysosomal permeabilization is Bid dependent. After tumor necrosis factor alpha/actinomycin D treatment, caspase 2 activity increased severalfold in wild-type hepatocytes, whereas minimal activity was observed in hepatocytes from cathepsin B knockout mice or in hepatoma cells treated with a cathepsin B inhibitor. In contrast, Bax was activated independently of cathepsin B. Pharmacological, genetic, or small interfering RNA-mediated inhibition of caspase 2 attenuated tumor necrosis factor alpha-mediated mitochondrial dysfunction, downstream caspase activation, and hepatocyte apoptosis. Conclusions: These data suggest that tumor necrosis factor alpha triggers Bid-dependent lysosomal permeabilization, followed by release of cathepsin B into the cytosol and activation of caspase 2. Caspase 2 then facilitates efficient mitochondrial cytochrome c release and apoptosis.
MeSH term(s)	Animals ; Apoptosis/physiology ; BH3 Interacting Domain Death Agonist Protein ; Carrier Proteins/metabolism ; Caspase 2 ; Caspases/genetics ; Caspases/metabolism ; Cathepsin B/metabolism ; Cells, Cultured ; Cytochromes c/metabolism ; Cytosol/enzymology ; Hepatocytes/cytology ; Hepatocytes/metabolism ; Lysosomes/enzymology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/metabolism ; RNA, Small Interfering ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	BH3 Interacting Domain Death Agonist Protein ; Bid protein, mouse ; Carrier Proteins ; RNA, Small Interfering ; Tumor Necrosis Factor-alpha ; Cytochromes c (9007-43-6) ; Caspase 2 (EC 3.4.22.-) ; Caspases (EC 3.4.22.-) ; Cathepsin B (EC 3.4.22.1)
Language	English
Publishing date	2005-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2005.05.022
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