Source:http://linkedlifedata.com/resource/pubmed/id/14512878
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
|
pubmed:dateCreated |
2003-9-26
|
pubmed:abstractText |
Heme oxygenase-1 (HO-1), a stress-responsive enzyme that catabolizes heme into carbon monoxide (CO), biliverdin, and iron, has previously been shown to protect grafts from ischemia/reperfusion injury and rejection. Here we investigated the protective potential of HO-1 in 5 models of immune-mediated liver injury. We found that up-regulation of endogenous HO-1 by cobalt-protoporphyrin-IX (CoPP) protected mice from apoptotic liver damage induced by anti-CD95 antibody (Ab) or d-galactosamine in combination with either anti-CD3 Ab, lipopolysaccharide (LPS), or tumor necrosis factor alpha (TNF-alpha). HO-1 induction prevented apoptotic liver injury, measured by inhibition of caspase 3 activation, although it did not protect mice from caspase-3-independent necrotic liver damage caused by concanavalin A (Con A) administration. In addition, overexpression of HO-1 by adenoviral gene transfer resulted in protection from apoptotic liver injury, whereas inhibition of HO-1 enzymatic activity by tin-protoporphyrin-IX (SnPP) abrogated the protective effect. HO-1-mediated protection seems to target parenchymal liver cells directly because CoPP treatment protected isolated primary hepatocytes from anti-CD95-induced apoptosis in vitro. Furthermore, depletion of Kupffer cells (KCs) did not interfere with the protective effect in vivo. Exogenous CO administration or treatment with the CO-releasing agent methylene chloride mimicked the protective effect of HO-1, whereas treatment with exogenous biliverdin or overexpression of ferritin by recombinant adenoviral gene transfer did not. In conclusion, HO-1 is a potent protective factor for cytokine- and CD95-mediated apoptotic liver damage. Induction of HO-1 might be of a therapeutic modality for inflammatory liver diseases.
|
pubmed:commentsCorrections | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carbon Monoxide,
http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase (Decyclizing),
http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase-1,
http://linkedlifedata.com/resource/pubmed/chemical/Hmox1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins
|
pubmed:status |
MEDLINE
|
pubmed:month |
Oct
|
pubmed:issn |
0270-9139
|
pubmed:author |
pubmed-author:EschenhagenThomasT,
pubmed-author:KaczmarekElzbietaE,
pubmed-author:RitterThomasT,
pubmed-author:SassGabrieleG,
pubmed-author:SeyfriedStefanS,
pubmed-author:SoaresMiguel Che ParreiraMC,
pubmed-author:TiegsGisaG,
pubmed-author:VolkHans-DieterHD,
pubmed-author:YamashitaKenichiroK,
pubmed-author:ZimmermannWolfram-HubertusWH
|
pubmed:issnType |
Print
|
pubmed:volume |
38
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
909-18
|
pubmed:dateRevised |
2006-11-15
|
pubmed:meshHeading |
pubmed-meshheading:14512878-Adenoviridae,
pubmed-meshheading:14512878-Animals,
pubmed-meshheading:14512878-Apoptosis,
pubmed-meshheading:14512878-Carbon Monoxide,
pubmed-meshheading:14512878-Enzyme Induction,
pubmed-meshheading:14512878-Gene Therapy,
pubmed-meshheading:14512878-Heme Oxygenase (Decyclizing),
pubmed-meshheading:14512878-Heme Oxygenase-1,
pubmed-meshheading:14512878-Hepatocytes,
pubmed-meshheading:14512878-Inflammation,
pubmed-meshheading:14512878-Liver,
pubmed-meshheading:14512878-Membrane Proteins,
pubmed-meshheading:14512878-Mice,
pubmed-meshheading:14512878-Mice, Inbred BALB C
|
pubmed:year |
2003
|
pubmed:articleTitle |
Heme oxygenase-1 and its reaction product, carbon monoxide, prevent inflammation-related apoptotic liver damage in mice.
|
pubmed:affiliation |
Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Fahrstrasse 17, D-91054 Erlangen, Germany.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|