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′...
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| Format: | Article |
| Language: | English |
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Wiley
2007-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2007/15481 |
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| 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 |
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| 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 |
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