Source:http://linkedlifedata.com/resource/pubmed/id/16901605
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2-3
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| pubmed:dateCreated |
2006-8-29
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| pubmed:abstractText |
In this study, we measured and characterized the bifunctional effects of a newly identified natural compound-bisindigotin (SLY-1), isolated from leaf extracts of Isatis indigotica, to CYP1A1/EROD activities in H4IIE cells. The compound, SLY-1 (1muM) elicited a transitory and significant induction of CYP1A1 RNA/protein levels and EROD activities in the cells. Maximum levels of CYP1A1 expression and EROD induction were attained at 8 and 12h of post-treatment, respectively. Thereafter the induction decreased significantly. Similar profile of CYP1A2 and CYP1B1 mRNA induction was observed. In contrast TCDD elicited CYP1A1/EROD induction was persistent. The transitory effect by SLY-1 is most likely due to the clearance of SLY-1 by cellular metabolism. Taken together the observation indicated that SLY-1 is an Ah receptor agonist for CYP1A1/CYP1A2/CYP1B1/EROD induction. Interestingly in the TCDD/SLY-1 cotreatment study, although synergistic effects on CYP1A1 expression and EROD induction were observed at 4-8h, significant inhibitory effects to TCDD induced CYP1A1 protein and EROD activity were detected at 12-24h of post-treatment. Because there was no significant reduction of CYP1A1, CYP1A2 or CYP1B1 transcript levels between TCDD- and TCDD/SLY-1 treated cells, the data pointed to the translational and/or post-translational inhibitory effect. The cellular signal transduction system may be modulated following exposure to SLY-1. To investigate the possible mechanisms involved, various specific kinase inhibitors or activators (chelerythrin, PD98059, U0126, ZM336372, SB202190, PKA inhibitor PKI (6-22) amide, and dbcAMP) were used for the assessment. Chelerythrine, PD98059 or dbcAMP treatment in TCDD induced cells showed significant inhibitory effects on CYP1A1 mRNA/protein expressions and EROD activities. U0126 had no observable EROD inhibitory effect. ZM336372 or SB202190 showed inhibition only at EROD activities. The results indicated that the SLY-1 inhibitory effect was possibly not mediated by the cAMP/PKA, PKC or MEK pathways. Nevertheless our results indicate that SLY-1 is not only an inducer of the CYP1A1 system, but also a potent inhibitor of CYP1A1 enzyme.
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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/Aryl Hydrocarbon Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/Benzo(a)pyrene,
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/Enzyme Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glyceraldehyde-3-Phosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrachlorodibenzodioxin,
http://linkedlifedata.com/resource/pubmed/chemical/cytochrome P-450 CYP1B1,
http://linkedlifedata.com/resource/pubmed/chemical/indigo
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
0300-483X
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
21
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| pubmed:volume |
226
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
188-96
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:16901605-Animals,
pubmed-meshheading:16901605-Aryl Hydrocarbon Hydroxylases,
pubmed-meshheading:16901605-Benzo(a)pyrene,
pubmed-meshheading:16901605-Blotting, Western,
pubmed-meshheading:16901605-Carcinoma, Hepatocellular,
pubmed-meshheading:16901605-Cell Line,
pubmed-meshheading:16901605-Cell Line, Tumor,
pubmed-meshheading:16901605-Cytochrome P-450 CYP1A1,
pubmed-meshheading:16901605-Cytochrome P-450 CYP1A2,
pubmed-meshheading:16901605-Enzyme Activators,
pubmed-meshheading:16901605-Enzyme Induction,
pubmed-meshheading:16901605-Enzyme Inhibitors,
pubmed-meshheading:16901605-Glyceraldehyde-3-Phosphate Dehydrogenases,
pubmed-meshheading:16901605-Indoles,
pubmed-meshheading:16901605-Isatis,
pubmed-meshheading:16901605-Phosphotransferases,
pubmed-meshheading:16901605-RNA, Messenger,
pubmed-meshheading:16901605-Rats,
pubmed-meshheading:16901605-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16901605-Tetrachlorodibenzodioxin
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| pubmed:year |
2006
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| pubmed:articleTitle |
Bifunctional modulating effects of an indigo dimer (bisindigotin) to CYP1A1 induction in H4IIE cells.
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| pubmed:affiliation |
Croucher Institute of Environmental Sciences and Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong, PR China.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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