Source:http://linkedlifedata.com/resource/pubmed/id/19085910
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2009-1-5
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pubmed:abstractText |
Carbon monoxide (CO) is a stress-inducible gas generated by heme oxygenase (HO) eliciting adaptive responses against toxicants; however, mechanisms for its reception remain unknown. Serendipitous observation in metabolome analysis in CO-overproducing livers suggested roles of cystathionine beta-synthase (CBS) that rate-limits transsulfuration pathway and H(2)S generation, for the gas-responsive receptor. Studies using recombinant CBS indicated that CO binds to the prosthetic heme, stabilizing 6-coordinated CO-Fe(II)-histidine complex to block the activity, whereas nitric oxide (NO) forms 5-coordinated structure without inhibiting it. The CO-overproducing livers down-regulated H(2)S to stimulate HCO(3) (-)-dependent choleresis: these responses were attenuated by blocking HO or by donating H(2)S. Livers of heterozygous CBS knockout mice neither down-regulated H(2)S nor exhibited the choleresis while overproducing CO. In the mouse model of estradiol-induced cholestasis, CO overproduction by inducing HO-1 significantly improved the bile output through stimulating HCO(3) (-) excretion; such a choleretic response did not occur in the knockout mice. Conclusion: Results collected from metabolome analyses suggested that CBS serves as a CO-sensitive modulator of H(2)S to support biliary excretion, shedding light on a putative role of the enzyme for stress-elicited adaptive response against bile-dependent detoxification processes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1527-3350
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pubmed:author |
pubmed-author:GodaNobuhitoN,
pubmed-author:HishikiTakakoT,
pubmed-author:IkedaSatsukiS,
pubmed-author:IshikawaKazuoK,
pubmed-author:IwabuchiTakuyaT,
pubmed-author:KajimuraMayumiM,
pubmed-author:KatoYuichiroY,
pubmed-author:KitagawaYukoY,
pubmed-author:MatsumotoKenjiK,
pubmed-author:SakuragawaTadayukiT,
pubmed-author:ShintaniTsunehiroT,
pubmed-author:SogaTomoyoshiT,
pubmed-author:SuematsuMakotoM,
pubmed-author:TakanoNaoharuN,
pubmed-author:UenoYukiY,
pubmed-author:YamamotoTakehiroT
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pubmed:issnType |
Electronic
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pubmed:volume |
49
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
141-50
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pubmed:meshHeading | |
pubmed:year |
2009
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pubmed:articleTitle |
Cystathionine beta-synthase as a carbon monoxide-sensitive regulator of bile excretion.
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pubmed:affiliation |
Department of Biochemistry and Integrative Medical Biology, Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
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pubmed:publicationType |
Journal Article
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