| 論文名 |
Progressive stages of mitochondrial destruction caused by cell toxic bile salts. |
| 著者 |
Sabine Schulz
Sabine Schmitt
Ralf Wimmer
Michaela Aichler
Sabine Eisenhofer
Josef Lichtmannegger
Carola Eberhagen
Renate Artmann
Ferenc Tookos
Axel Walch
Daniel Krappmann
Catherine Brenner
Christian Rust
Hans Zischka
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| キーワード |
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| 出版年月 |
1970年1月 |
| 発表先 |
Biochim Biophys Acta. 2013 Sep;1828(9):2121-33. |
| WEBサイト |
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| 論文概要（和文） |
細胞毒性の胆汁酸塩によって引き起こされるミトコンドリア破壊の進行段階。 |
| 論文概要（英文） |
The cell-toxic bile salt glycochenodeoxycholic acid (GCDCA) and taurochenodeoxycholic acid (TCDCA) are responsible for hepatocyte demise in cholestatic liver diseases, while tauroursodeoxycholic acid (TUDCA) is regarded hepatoprotective. We demonstrate the direct mitochondrio-toxicity of bile salts which deplete the mitochondrial membrane potential and induce the mitochondrial permeability transition (MPT). The bile salt mediated mechanistic mode of destruction significantly differs from that of calcium, the prototype MPT inducer. Cell-toxic bile salts initially bind to the mitochondrial outer membrane. Subsequently, the structure of the inner boundary membrane disintegrates. And it is only thereafter that the MPT is induced. This progressive destruction occurs in a dose- and time-dependent way. We demonstrate that GCDCA and TCDCA, but not TUDCA, preferentially permeabilize liposomes containing the mitochondrial membrane protein ANT, a process resembling the MPT induction in whole mitochondria. This suggests that ANT is one decisive target for toxic bile salts. To our knowledge this is the first report unraveling the consecutive steps leading to mitochondrial destruction by cell-toxic bile salts. |
