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Article: Bifunctional modulating effects of an indigo dimer (bisindigotin) to CYP1A1 induction in H4IIE cells

TitleBifunctional modulating effects of an indigo dimer (bisindigotin) to CYP1A1 induction in H4IIE cells
Authors
Issue Date2006
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/toxicol
Citation
Toxicology, 2006, v. 226 n. 2-3, p. 188-196 How to Cite?
AbstractIn 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 (1 μM) 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 12 h 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 4-8 h, significant inhibitory effects to TCDD induced CYP1A1 protein and EROD activity were detected at 12-24 h 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. © 2006 Elsevier Ireland Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/183395
ISSN
2015 Impact Factor: 3.817
2015 SCImago Journal Rankings: 1.335
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLai, KPen_US
dc.contributor.authorMak, NKen_US
dc.contributor.authorWei, Xen_US
dc.contributor.authorWong, RNSen_US
dc.contributor.authorWong, MHen_US
dc.contributor.authorWong, CKCen_US
dc.date.accessioned2013-05-27T07:12:32Z-
dc.date.available2013-05-27T07:12:32Z-
dc.date.issued2006en_US
dc.identifier.citationToxicology, 2006, v. 226 n. 2-3, p. 188-196en_US
dc.identifier.issn0300-483Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/183395-
dc.description.abstractIn 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 (1 μM) 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 12 h 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 4-8 h, significant inhibitory effects to TCDD induced CYP1A1 protein and EROD activity were detected at 12-24 h 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. © 2006 Elsevier Ireland Ltd. All rights reserved.en_US
dc.languageengen_US
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/toxicolen_US
dc.relation.ispartofToxicologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAryl Hydrocarbon Hydroxylases - Biosynthesisen_US
dc.subject.meshBenzo(A)Pyrene - Metabolismen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCarcinoma, Hepatocellular - Enzymologyen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCytochrome P-450 Cyp1a1 - Antagonists & Inhibitors - Biosynthesis - Metabolismen_US
dc.subject.meshCytochrome P-450 Cyp1a2 - Biosynthesisen_US
dc.subject.meshEnzyme Activators - Pharmacologyen_US
dc.subject.meshEnzyme Induction - Drug Effectsen_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshGlyceraldehyde-3-Phosphate Dehydrogenases - Metabolismen_US
dc.subject.meshIndoles - Pharmacologyen_US
dc.subject.meshIsatis - Chemistryen_US
dc.subject.meshPhosphotransferases - Antagonists & Inhibitorsen_US
dc.subject.meshRna, Messenger - Biosynthesis - Geneticsen_US
dc.subject.meshRatsen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshTetrachlorodibenzodioxin - Pharmacologyen_US
dc.titleBifunctional modulating effects of an indigo dimer (bisindigotin) to CYP1A1 induction in H4IIE cellsen_US
dc.typeArticleen_US
dc.identifier.emailLai, KP: ballllai@hotmail.comen_US
dc.identifier.authorityLai, KP=rp01753en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.tox.2006.06.016en_US
dc.identifier.pmid16901605-
dc.identifier.scopuseid_2-s2.0-33747869617en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33747869617&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume226en_US
dc.identifier.issue2-3en_US
dc.identifier.spage188en_US
dc.identifier.epage196en_US
dc.identifier.isiWOS:000240862400013-
dc.publisher.placeIrelanden_US
dc.identifier.scopusauthoridLai, KP=7402135707en_US
dc.identifier.scopusauthoridMak, NK=35587830100en_US
dc.identifier.scopusauthoridWei, X=7402117173en_US
dc.identifier.scopusauthoridWong, RNS=7402126957en_US
dc.identifier.scopusauthoridWong, MH=7403908633en_US
dc.identifier.scopusauthoridWong, CKC=35276549400en_US

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