The involvement of endoplasmic reticulum stress in bile acid-induced hepatocellular injury.
The involvement of endoplasmic reticulum stress in bile acid-induced hepatocellular injury.
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DOI：
10.3164/jcbn.13-46
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发表时间：
2014-03
影响因子：
2.4
通讯作者：
Hara H
中科院分区：
文献类型：
--
作者：
Adachi T;Kaminaga T;Yasuda H;Kamiya T;Hara H
由肠道细菌产生的次级胆汁酸在肝肠循环中积累到高水平，并可能导致肝细胞损伤的发病机制。相对疏水性已被认为是这些化合物的生物学特性的一个重要决定因素，尽管胆汁酸诱导发病机制尚未完全了解。另一方面，内质网应激已被证明参与各种致病条件的诱导和发展。在这份报告中，我们证明，在HepG 2细胞的细胞毒性和内质网应激的强度所测试的胆汁酸触发在很大程度上取决于它们的疏水性。鹅去氧胆酸处理后caspase-3的激活和DNA片段化表明细胞凋亡对细胞毒性的贡献。细胞内钙离子水平的增加和鹅去氧胆酸处理刺激的活性氧的产生有助于内质网应激。胆汁酸还诱导转化生长因子-β，一种有效的促纤维化因子，已知其诱导肝细胞凋亡并最终诱导肝纤维化。总之，我们的研究表明，胆汁酸诱导内质网应激，这反过来又刺激HepG 2细胞凋亡，在疏水性依赖的方式。
Secondary bile acids produced by enteric bacteria accumulate to high levels in the enterohepatic circulation and may contribute to the pathogenesis of hepatocellular injury. Relative hydrophobicity has been suggested to be an important determinant of the biological properties of these compounds, although the mechanism by which bile acids induce pathogenesis is not fully understood. On the other hand, endoplasmic reticulum stress has been shown to be involved in the induction and development of various pathogenic conditions. In this report, we demonstrated that the intensities of cytotoxicity and endoplasmic reticulum stress in HepG2 cells triggered by the bile acids tested were largely dependent on their hydrophobicity. The activation of caspase-3 and DNA fragmentation by treatment with chenodeoxycholic acid showed the contribution of apoptosis to cytotoxicity. Increases in intracellular calcium levels and the generation of reactive oxygen species stimulated by treatment with chenodeoxycholic acid contributed to endoplasmic reticulum stress. Bile acids also induced transforming growth factor-β, a potent profibrogenic factor, which is known to induce hepatocyte apoptosis and ultimately liver fibrosis. In conclusion, our study demonstrated that bile acids induced endoplasmic reticulum stress, which in turn stimulated apoptosis in HepG2 cells, in a hydrophobicity-dependent manner.
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影响因子：
4.1
作者：
Powell, AA;LaRue, JM;Martinez, JD
通讯作者：
Martinez, JD
影响因子：
5.5
作者：
Duan, Yuntao;Gross, Robert A.;Sheu, Shey-Shing
通讯作者：
Sheu, Shey-Shing
影响因子：
2.9
作者：
Leindler, L;Morschl, É;Farkas, G
通讯作者：
Farkas, G
DOI：
10.1152/ajpgi.00482.2007
发表时间：
2008-02-01
影响因子：
4.5
作者：
Tamaki, Nobuyuki;Hatano, Etsuro;Uemoto, Shinji
通讯作者：
Uemoto, Shinji
影响因子：
10.5
作者：
Marciniak, SJ;Yun, CY;Ron, D
通讯作者：
Ron, D