Source:http://linkedlifedata.com/resource/pubmed/id/18657588
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2-3
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| pubmed:dateCreated |
2008-8-29
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| pubmed:abstractText |
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic accumulation of biliverdin and its monoglucuronide in moderately TCDD-resistant line B rats, but not in highly TCDD-resistant line A rats. In the mammalian heme degradation process, heme is cleaved to biliverdin by the rate-limiting enzyme heme oxygenase-1 (HO-1). Subsequently, biliverdin IXalpha reductase (BVRA) catalyzes the reduction of biliverdin to bilirubin. In heme biosynthesis, the rate-limiting enzyme is delta-aminolevulinic acid synthetase 1 (ALAS1). The effect of TCDD on HO-1, BVRA and ALAS1 was studied at the levels of mRNA (all three enzymes), protein expression (HO-1), and enzymatic activity (BVRA, liver only) in order to determine whether the accumulation of biliverdin could be due to their altered expression. In both lines A and B, 300 microg/kg TCDD transiently repressed hepatic HO-1 mRNA on day 2 but induced HO-1 protein expression at later time-points; however, the impact emerged earlier (day 14 vs. day 35) in line B rats. In spleen, TCDD repressed HO-1 mRNA and protein expression in lines A and B through days 2-35, but did not affect its mRNA levels in TCDD-sensitive L-E rats (10 days after 100 microg/kg). In all rat strains/lines, there was a strong repression of ALAS1 and a moderate induction of BVRA mRNA in liver, but mostly not in spleen. Hepatic BVRA activity was increased in lines A and B on day 14. At 5 weeks, it was still elevated in line A but reduced to 51% of control in line B. The results suggest that hepatic heme degradation is induced by TCDD in rats; however, this does not alone explain the accumulation of biliverdin in line B rats. Other factors such as the late repression of BVRA found here and possibly oxidative stress may be important contributors to biliverdin accumulation in these rats.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5-Aminolevulinate Synthetase,
http://linkedlifedata.com/resource/pubmed/chemical/Biliverdine,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP1A1,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP1A2,
http://linkedlifedata.com/resource/pubmed/chemical/Heme,
http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase-1,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases Acting on CH-CH...,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Aryl Hydrocarbon,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrachlorodibenzodioxin,
http://linkedlifedata.com/resource/pubmed/chemical/biliverdin reductase
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
|
| pubmed:issn |
0300-483X
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
4
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| pubmed:volume |
250
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
132-42
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| pubmed:meshHeading |
pubmed-meshheading:18657588-5-Aminolevulinate Synthetase,
pubmed-meshheading:18657588-Animals,
pubmed-meshheading:18657588-Biliverdine,
pubmed-meshheading:18657588-Body Weight,
pubmed-meshheading:18657588-Cloning, Molecular,
pubmed-meshheading:18657588-Cytochrome P-450 CYP1A1,
pubmed-meshheading:18657588-Cytochrome P-450 CYP1A2,
pubmed-meshheading:18657588-Female,
pubmed-meshheading:18657588-Heme,
pubmed-meshheading:18657588-Heme Oxygenase-1,
pubmed-meshheading:18657588-Liver,
pubmed-meshheading:18657588-Oxidoreductases Acting on CH-CH Group Donors,
pubmed-meshheading:18657588-RNA,
pubmed-meshheading:18657588-RNA, Messenger,
pubmed-meshheading:18657588-Rats,
pubmed-meshheading:18657588-Receptors, Aryl Hydrocarbon,
pubmed-meshheading:18657588-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:18657588-Tetrachlorodibenzodioxin
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| pubmed:year |
2008
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| pubmed:articleTitle |
Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on heme oxygenase-1, biliverdin IXalpha reductase and delta-aminolevulinic acid synthetase 1 in rats with wild-type or variant AH receptor.
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| pubmed:affiliation |
Department of Environmental Health, National Public Health Institute, Box 95, FI-70701 Kuopio, Finland. marjo.niittynen@ktl.fi
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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