Effects of Endocrine Disrupting Chemicals on Amphibian Metamorphosis and Mitochondrial Membrane Permeability Transition

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概要

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• The estrogenic chemical bisphenol A (BPA) has multiple hormonal activities, but its effects on thyroid hormone (TH) action are not fully understood. TH is required for the metamorphosis of tadpoles into frogs, and thus tadpole tail regression, one of the most spectacular events in metamorphosis, can be used for studying the effect of BPA and related compounds (BPAs) on TH action. We found that 3,3',5-triiodothyronine (T_3)-induced tadpole tail regression in the wrinkled frog Rana rugosa (R. rugosa) is suppressed by BPA, tetrabromobisphenol A (TBBPA), tetrachlorobisphenol A (TCBPA), and tetramethylbisphenol A (TMBPA). BPAs also inhibited spontaneous metamorphosis in the tropical clawed frog Silurana tropicalis (S. tropicalis) controlled by endogenous circulating TH. These results indicate that BPAs are TH antagonists. For the African clawed frog Xenopus laevis (X. laevis), transgenic tadpoles carrying plasmid DNA containing TH response element (TRE) and 5'-upstream promoter region of the TH receptor (TR)βA1 gene linked to an enhanced green fluorescent protein (EGFP) gene, T_3 induced a strong EGFP expression in the hind limbs. This expression was suppressed by BPA, TBBPA, TCBPA and TMBPA, suggesting BPAs all act as antagonists to prevent the binding of T_3 to TR, resulting in inhibition of TR-mediated gene expression. Much work has been done in examining the apoptotic and other detrimental effects of polychlorinated biphenyls (PCBs), but the role of mitochondrial damage in such toxic action remains obscure. There is evidence however that mitochondrial membrane permeability transition (MPT) plays a crucial role in apoptosis. We investigated the effect of 4-hydroxy-3,3',4',5-tetrachlorobiphenyl (4-OH-TCB) on isolated rat liver mitochondria. In order to help clarify this, biochemical analysis revealed that 4-OH-TCB induced calcium release, reactive oxygen species (ROS) generation, depolarization, swelling and cytochrome c (Cyt. c) release in a time- and concentration-dependent manner. These 4-OH-TCB-induced changes in mitochondrial function were found to be inhibited by the presence of cyclosporin A (CsA), a specific inhibitor of MPT, suggesting a classic type of MPT. It is concluded that 4-OH-TCB induces MPT together with ROS generation, causing apoptosis in certain cells.

• 公益社団法人日本薬学会の論文
• 2008-06-01

著者

• OHTA Shigeru

  Graduate School of Biomedical Sciences, Hiroshima University

• KASHIWAGI Keiko

  Institute for Amphibian Biology, Graduate School of Science, Hiroshima University

• KASHIWAGI Akihiko

  Institute for Amphibian Biology, Graduate School of Science, Hiroshima University

• Kashiwagi Akihiko

  Div. Of Embryology And Genetics Inst. For Amphibian Biology Graduate School Of Sci. Hiroshima Univ.

• Shigeyuki Kitamura

  Nihon Pharmaceutical University

• Kitamura Shigeyuki

  広島大学 医学部総合薬学科生体機能分子動態学

• Kitamura Shigeyuki

  広島大学 総合薬

• Kitamura Shigeyuki

  広島大学原爆放射能医学研究所

• Hanada Hideki

  Div. Of Embryology And Genetics Inst. For Amphibian Biology Graduate School Of Sci. Hiroshima Univ.

• Hanada Hideki

  広島大学 理学研究科

• Hanada Hideki

  Institute For Amphibian Biology Graduate School Of Science Hiroshima University

• Hanada H

  Hiroshima Univ. Higashihiroshima Jpn

• Kitamura Shigeyuki

  Nihon Pharmaceutical University

• Sugihara Kazumi

  Graduate School of Biomedical Sciences, Hiroshima University

• Utsumi Kozo

  Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and

• Utsumi K

  Department Of Cytology And Histology Okayama University Graduate School Of Medicine Dentistry And Ph

• Utsumi Kozo

  Department Of Biochemistry Cancer Institute Okayama University Medical School

• Sugihara K

  Graduate School Of Biomedical Sciences Hiroshima University

• Ohta S

  Graduate School Of Biomedical Sciences Hiroshima University

• Kadokami Kiwao

  Committee of Kitakyusyu City on Effects of Endocrine-Disrupting Chemicals on Wildlife

• Utsumi Kozo

  Department Of Cytology And Histology Okayama University Graduate School Of Medicine Dentistry And Ph

• Utsumi Kozo

  Dep. Of Cytology And Histology Okayama Univ. Graduate School Of Medicine Dentistry And Pharmaceutica

• Kashiwagi Akihiko

  Institute For Amphibian Biology Graduate School Of Science Hiroshima University

• Kitamura Shigeyuki

  Institute Of Pharmaceutical Science. Hiroshima University School Of Medicine

• Kashiwagi A

  Div. Of Embryology And Genetics Inst. For Amphibian Biology Graduate School Of Sci. Hiroshima Univ.

• Kashiwagi K

  Life Sci. Inst. Sophia Univ.

• Ohta Shigeru

  Graduate School Of Biomedical Sciences Hiroshima Univ.

• Kashiwagi Keiko

  Div. Of Embryology And Genetics Inst. For Amphibian Biology Graduate School Of Sci. Hiroshima Univ.

• Kashiwagi Keiko

  Institute For Amphibian Biology Graduate School Of Science Hiroshima University

• SUGIHARA Kazumi

  Graduate School of Biomedical and Health Sciences, Hiroshima University

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