Suppression of Peroxisomal Enzyme Activities and Cytochrome P450 4A Isozyme Expression by Congeneric Polybrominated and Polychlorinated Biphenyls

The purpose of this study was to determine the effects of PCBs and PBBs on peroxisome proliferator-activated receptor-α-(PPARα-) associated enzyme activities or protein levels. Male Sprague-Dawley rats were administered a single IP injection (150 μmol/kg) of either 3,3′,4,4′-tetrabromobiphenyl, 3,3′...

Full description

Saved in:
Bibliographic Details
Main Authors: Larry W. Robertson, Isabelle Berberian, Tim Borges, Li-Chuan Chen, Ching K. Chow, Howard P. Glauert, Johannes G. Filser, Helmut Thomas
Format: Article
Language:English
Published: Wiley 2007-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2007/15481
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850173861446811648
author Larry W. Robertson
Isabelle Berberian
Tim Borges
Li-Chuan Chen
Ching K. Chow
Howard P. Glauert
Johannes G. Filser
Helmut Thomas
author_facet Larry W. Robertson
Isabelle Berberian
Tim Borges
Li-Chuan Chen
Ching K. Chow
Howard P. Glauert
Johannes G. Filser
Helmut Thomas
author_sort Larry W. Robertson
collection DOAJ
description The purpose of this study was to determine the effects of PCBs and PBBs on peroxisome proliferator-activated receptor-α-(PPARα-) associated enzyme activities or protein levels. Male Sprague-Dawley rats were administered a single IP injection (150 μmol/kg) of either 3,3′,4,4′-tetrabromobiphenyl, 3,3′,4,4′-tetrachlorobiphenyl, 3,3′,5,5′-tetrabromobiphenyl, 2′,3,3′,4,5-pentachlorobiphenyl, 3,3′,4,4′,5-pentachlorobiphenyl, 2,2′,3,3′,5,5′-hexachlorobiphenyl, or 3,3′,4,4′,5,5′-hexabromobiphenyl in corn oil (10 ml/kg). One week later, the activities of catalase, peroxisomal fatty acyl-CoA oxidase, and peroxisomal beta-oxidation as well as cytochrome P450 4A (CYP4A) protein content were determined in subcellular liver fractions. None of the peroxisomal enzyme activities were significantly increased by any of the halogenated biphenyl congeners tested. Except for minor (approx. 25%) increases in the total CYP4A content following treatment with 2,2′,3,3′,5,5′-hexachlorobiphenyl and 3,3′,5,5′-tetrabromobiphenyl, CYP4A protein contents were not increased by any treatment. The two Ah receptor agonists, 3,3′,4,4′-tetrabromobiphenyl and 3,3′,4,4′,5-pentachlorobiphenyl, significantly diminished the liver content of CYP4A proteins and activities of the peroxisomal enzymes studied. Since a range of congeners with different biologic and toxicologic activities were selected for this study, it may be concluded that the polyhalogenated biphenyls do not induce peroxisome proliferation in the male rat, but rather certain members of this class of compounds down regulate peroxisome-associated enzymes. Since PCBs and PBBs do not increase enzyme activities and expression of proteins associated with PPARα, these agents are therefore exerting their carcinogenic and promoting activities by some other mechanism.
format Article
id doaj-art-d3fccd4365ea4b36bc2e77f039e2299c
institution OA Journals
issn 1687-4757
1687-4765
language English
publishDate 2007-01-01
publisher Wiley
record_format Article
series PPAR Research
spelling doaj-art-d3fccd4365ea4b36bc2e77f039e2299c2025-08-20T02:19:45ZengWileyPPAR Research1687-47571687-47652007-01-01200710.1155/2007/1548115481Suppression of Peroxisomal Enzyme Activities and Cytochrome P450 4A Isozyme Expression by Congeneric Polybrominated and Polychlorinated BiphenylsLarry W. Robertson0Isabelle Berberian1Tim Borges2Li-Chuan Chen3Ching K. Chow4Howard P. Glauert5Johannes G. Filser6Helmut Thomas7Graduate Center for Toxicology, University of Kentucky, Funkhouser Building, Lexington, KY 40506-0054, USAGraduate Center for Toxicology, University of Kentucky, Funkhouser Building, Lexington, KY 40506-0054, USAGraduate Center for Toxicology, University of Kentucky, Funkhouser Building, Lexington, KY 40506-0054, USAGraduate Center for Toxicology, University of Kentucky, Funkhouser Building, Lexington, KY 40506-0054, USAGraduate Center for Toxicology, University of Kentucky, Funkhouser Building, Lexington, KY 40506-0054, USAGraduate Center for Toxicology, University of Kentucky, Funkhouser Building, Lexington, KY 40506-0054, USAGSF-National Research Center For Environment and Health, Institute of Toxicology, Ingolstädter Landstraße 1, Neuherberg 85716, GermanyTranzyme Pharma Inc., 3001 12th Avenue North, Building Z5-3037, Sherbrooke, QC J1H 5N4, CanadaThe purpose of this study was to determine the effects of PCBs and PBBs on peroxisome proliferator-activated receptor-α-(PPARα-) associated enzyme activities or protein levels. Male Sprague-Dawley rats were administered a single IP injection (150 μmol/kg) of either 3,3′,4,4′-tetrabromobiphenyl, 3,3′,4,4′-tetrachlorobiphenyl, 3,3′,5,5′-tetrabromobiphenyl, 2′,3,3′,4,5-pentachlorobiphenyl, 3,3′,4,4′,5-pentachlorobiphenyl, 2,2′,3,3′,5,5′-hexachlorobiphenyl, or 3,3′,4,4′,5,5′-hexabromobiphenyl in corn oil (10 ml/kg). One week later, the activities of catalase, peroxisomal fatty acyl-CoA oxidase, and peroxisomal beta-oxidation as well as cytochrome P450 4A (CYP4A) protein content were determined in subcellular liver fractions. None of the peroxisomal enzyme activities were significantly increased by any of the halogenated biphenyl congeners tested. Except for minor (approx. 25%) increases in the total CYP4A content following treatment with 2,2′,3,3′,5,5′-hexachlorobiphenyl and 3,3′,5,5′-tetrabromobiphenyl, CYP4A protein contents were not increased by any treatment. The two Ah receptor agonists, 3,3′,4,4′-tetrabromobiphenyl and 3,3′,4,4′,5-pentachlorobiphenyl, significantly diminished the liver content of CYP4A proteins and activities of the peroxisomal enzymes studied. Since a range of congeners with different biologic and toxicologic activities were selected for this study, it may be concluded that the polyhalogenated biphenyls do not induce peroxisome proliferation in the male rat, but rather certain members of this class of compounds down regulate peroxisome-associated enzymes. Since PCBs and PBBs do not increase enzyme activities and expression of proteins associated with PPARα, these agents are therefore exerting their carcinogenic and promoting activities by some other mechanism.http://dx.doi.org/10.1155/2007/15481
spellingShingle Larry W. Robertson
Isabelle Berberian
Tim Borges
Li-Chuan Chen
Ching K. Chow
Howard P. Glauert
Johannes G. Filser
Helmut Thomas
Suppression of Peroxisomal Enzyme Activities and Cytochrome P450 4A Isozyme Expression by Congeneric Polybrominated and Polychlorinated Biphenyls
PPAR Research
title Suppression of Peroxisomal Enzyme Activities and Cytochrome P450 4A Isozyme Expression by Congeneric Polybrominated and Polychlorinated Biphenyls
title_full Suppression of Peroxisomal Enzyme Activities and Cytochrome P450 4A Isozyme Expression by Congeneric Polybrominated and Polychlorinated Biphenyls
title_fullStr Suppression of Peroxisomal Enzyme Activities and Cytochrome P450 4A Isozyme Expression by Congeneric Polybrominated and Polychlorinated Biphenyls
title_full_unstemmed Suppression of Peroxisomal Enzyme Activities and Cytochrome P450 4A Isozyme Expression by Congeneric Polybrominated and Polychlorinated Biphenyls
title_short Suppression of Peroxisomal Enzyme Activities and Cytochrome P450 4A Isozyme Expression by Congeneric Polybrominated and Polychlorinated Biphenyls
title_sort suppression of peroxisomal enzyme activities and cytochrome p450 4a isozyme expression by congeneric polybrominated and polychlorinated biphenyls
url http://dx.doi.org/10.1155/2007/15481
work_keys_str_mv AT larrywrobertson suppressionofperoxisomalenzymeactivitiesandcytochromep4504aisozymeexpressionbycongenericpolybrominatedandpolychlorinatedbiphenyls
AT isabelleberberian suppressionofperoxisomalenzymeactivitiesandcytochromep4504aisozymeexpressionbycongenericpolybrominatedandpolychlorinatedbiphenyls
AT timborges suppressionofperoxisomalenzymeactivitiesandcytochromep4504aisozymeexpressionbycongenericpolybrominatedandpolychlorinatedbiphenyls
AT lichuanchen suppressionofperoxisomalenzymeactivitiesandcytochromep4504aisozymeexpressionbycongenericpolybrominatedandpolychlorinatedbiphenyls
AT chingkchow suppressionofperoxisomalenzymeactivitiesandcytochromep4504aisozymeexpressionbycongenericpolybrominatedandpolychlorinatedbiphenyls
AT howardpglauert suppressionofperoxisomalenzymeactivitiesandcytochromep4504aisozymeexpressionbycongenericpolybrominatedandpolychlorinatedbiphenyls
AT johannesgfilser suppressionofperoxisomalenzymeactivitiesandcytochromep4504aisozymeexpressionbycongenericpolybrominatedandpolychlorinatedbiphenyls
AT helmutthomas suppressionofperoxisomalenzymeactivitiesandcytochromep4504aisozymeexpressionbycongenericpolybrominatedandpolychlorinatedbiphenyls