Partial characterization of cytoprotective mechanisms of lecithin against bile salt-induced bile duct damage
Partial characterization of cytoprotective mechanisms of lecithin against bile salt-induced bile duct damage
复制标题
卵磷脂对胆盐诱导的胆管损伤的细胞保护机制的部分表征
DOI：
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发表时间：
2004
影响因子：
6.3
通讯作者：
K. Chayama
中科院分区：
文献类型：
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作者：
K. Tsuboi;S. Tazuma;T. Nishioka;K. Chayama
背景我们最近发现环孢素A可引起胆汁脂质分泌不成比例的减少，而亲水性胆汁盐可通过增强胆汁卵磷脂分泌来抑制这种减少。在本研究中，亲水性胆汁盐的这种细胞保护作用的潜在机制被确定，注意卵磷脂的可能作用。方法永生化小鼠胆管细胞与疏水性胆汁盐的牛磺酸缀合物培养4 h（胆酸盐[TC]）和亲水性胆汁盐（熊去氧胆酸盐[TUDC]、β-尿苷胆酸盐[TβMC]和β-尿苷胆酸盐[TαMC]），200 µM，存在或不存在卵磷脂（5、10、25、50、100或200 µM），然后使用膜联蛋白V-异硫氰酸荧光素（FITC）/碘化丙啶（PI）染色进行流式细胞术检测细胞凋亡。逆转录-聚合酶链反应（RT-PCR）检测胆管细胞胆盐转运蛋白（顶端钠依赖性胆盐转运蛋白[Asbt]和多药耐药蛋白3 [Mrp 3]）的mRNA表达。有趣的是，胆盐诱导的细胞凋亡被卵磷脂以浓度依赖的方式抑制。此外，RT-PCR显示，Asbt和Mrp 3 mRNA的表达增强的所有的胆汁盐，而卵磷脂降低Asbt的表达，但增强Mrp 3 express.ConclusionsThese研究结果表明，胆汁盐引起胆管细胞损伤通过Asbt介导的摄取，但胆卵磷脂生理抑制这种损害通过减少这种转运蛋白的表达。此外，卵磷脂诱导Mrp 3表达可能在抑制胆汁蓄积中起作用。因此，调节卵磷脂分泌到胆汁中可能是治疗胆道疾病的另一个重要靶点。
BackgroundWe recently demonstrated that cyclosporine A causes a disproportionate reduction of biliary lipid secretion, and this is inhibited by hydrophilic bile salts through the enhancing of biliary lecithin secretion. In the present study, the underlying mechanism of such a cytoprotective action of hydrophilic bile salts was determined with attention to the possible role of lecithin.MethodsImmortalized mouse cholangiocytes were cultured for 4 h with taurine conjugates of a hydrophobic bile salt (cholate [TC]), and hydrophilic bile salts (ursodeoxycholate [TUDC], betamuricholate [TβMC], and alphamuricholate [TαMC]), at 200 µM, in the presence or absence of lecithin (5, 10, 25, 50, 100, or 200 µM), followed by flow cytometric detection of apoptosis, using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. Cholangiocyte bile salt transporter mRNAs (apical sodium-dependent bile-salt transporter [Asbt] and multidrug resistance protein 3 [Mrp3]) were determined by reverse transcription-polymerase chain reaction (RT-PCR).ResultsApoptosis was induced by all of the bile salts (TC > TUDC, TβMC, and TαMC). Interestingly, bile salt-induced apoptosis was inhibited by lecithin in a concentration-dependent manner. Further, RT-PCR showed that the expressions of Asbt and Mrp3 mRNAs were enhanced by all the bile salts, whereas lecithin reduced Asbt expression, but enhanced Mrp3 expression.ConclusionsThese findings indicate that bile salts cause bile-duct cell damage through Asbt-mediated uptake, but that biliary lecithin physiologically inhibits such damage by reducing the expression of this transporter. In addition, the induction of Mrp3 expression by lecithin may play a role in inhibiting the accumulation of bile. Thus, the modulation of lecithin secretion into bile may be another important target for the treatment of biliary disorders.
影响因子：
4.1
作者：
Powell, AA;LaRue, JM;Martinez, JD
通讯作者：
Martinez, JD
影响因子：
15.9
作者：
Faubion, WA;Guicciardi, ME;Gores, GJ
通讯作者：
Gores, GJ