| Deficiency of Bid protein reduces sepsis-induced apoptosis and inflammation, while improving septic survival. | |
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MedLine Citation:
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PMID: 20023601 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Increased apoptotic cell death is believed to play a pathological role in patients with sepsis and experimental animals. Apoptosis can be induced by either a cell death receptor (extrinsic) or a mitochondrial (intrinsic) pathway. Bid, a proapoptotic member of the Bcl-2 family, is thought to mediate the cross talk between the extrinsic and intrinsic pathways of apoptosis; however, little is known about the action of Bid in the development of apoptosis and organ-specific tissue damage/cell death as seen in polymicrobial sepsis. Our results show that after the onset of sepsis, tBid (the active form of Bid) is significantly increased in mitochondrial fractions of the thymus, spleen, Peyer patches, and liver, and that Fas or FasL deficiency blocks Bid activation in various tissues after septic challenge. Increased Bid activation is correlated with increased active caspase-3, caspase-9, and apoptosis during sepsis. Bid-deficient mice exhibit significantly reduced apoptosis in the thymus, spleen, and Peyer patches compared with background mice after sepsis. Furthermore, Bid-deficient mice had significantly reduced systemic and local inflammatory cytokine levels and improved survival after sepsis. These data support not only the contribution of Bid to sepsis-induced apoptosis and the onset of septic morbidity/mortality, but also the existence of a bridge between extrinsic apoptotic signals, e.g., FasL:Fas, TNF:TNFR, and so on, and the intrinsic mitochondrial pathway via Bid-tBid activation during sepsis. |
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Authors:
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Chun-Shiang Chung; Fabienne Venet; Yaping Chen; Leslie N Jones; Douglas C Wilson; Carol A Ayala; Alfred Ayala |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: 34 ISSN: 1540-0514 ISO Abbreviation: Shock Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-22 Completed Date: 2010-11-10 Revised Date: 2011-08-03 |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: United States |
Other Details:
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Languages: eng Pagination: 150-61 Citation Subset: IM |
Affiliation:
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Division of Surgical Research, Department of Surgery, Rhode Island Hospital, Providence, RI 02903, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alanine Transaminase
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blood Animals Apoptosis / physiology* BH3 Interacting Domain Death Agonist Protein / deficiency*, physiology Caspase 9 / metabolism Cytokines / metabolism Cytosol / metabolism Fas Ligand Protein / physiology Inflammation / immunology Liver / immunology Male Mice Mitochondria / metabolism Protein Transport Receptors, Tumor Necrosis Factor / physiology Sepsis / immunology*, mortality, pathology Signal Transduction / physiology Spleen / immunology |
| Grant Support | |
ID/Acronym/Agency:
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GM53209-10/GM/NIGMS NIH HHS; R01 GM053209-14/GM/NIGMS NIH HHS; R01 GM053209-16/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/BH3 Interacting Domain Death Agonist Protein; 0/Cytokines; 0/Fas Ligand Protein; 0/Receptors, Tumor Necrosis Factor; EC 2.6.1.2/Alanine Transaminase; EC 3.4.22.-/Caspase 9 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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