Differential modulation of cellular death and survival pathways by conjugated bile acids
Differential modulation of cellular death and survival pathways by conjugated bile acids
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DOI：
10.1186/1471-2091-2-11
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发表时间：
2001-01-01
期刊：
影响因子：
--
通讯作者：
Agellon, Luis B.
中科院分区：
文献类型：
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作者：
Torchia, Enrique C.;Stolz, Andrew;Agellon, Luis B.
背景：肝脏来源的 McNtcp。 24 细胞运输胆汁酸并对两类结合胆汁酸表现出独特的反应。牛磺酸结合胆汁酸无毒，而甘氨酸结合胆汁酸可有效诱导细胞凋亡。本研究的目的是确定差异敏感性是否仅限于正常转运胆汁酸的细胞，以及胆汁酸结合蛋白是否可以减少胆汁酸介导的细胞凋亡。在中国仓鼠卵巢（CHO）细胞中表达顶端钠/胆汁酸协同转运蛋白（asbt），以在非肝源性细胞模型（CHO.asbt）中建立主动胆汁酸转运。 McNtcp 表达高亲和力胆汁酸结合剂。 24个细胞。结果：McNtcp的耐受性。 24 细胞对牛磺酸结合的胆汁酸与磷脂酰肌醇 3-激酶 (PI3K) 活性的刺激有关。 CHO 的治疗。牛磺酸和甘氨酸结合胆汁酸的 asbt 细胞会导致细胞凋亡。与 McNtcp 不同。 24细胞中，CHO中的PI3K活性没有增加。用牛磺酸缀合胆汁酸处理的 asbt 细胞。胆汁酸结合剂的高水平表达并没有减弱 McNtcp 中胆汁酸诱导的细胞毒性。 24个细胞。结论：数据表明McNtcp。 24 细胞拥有一种机制，可以对不同类别的胆汁酸做出独特的反应。此外，涉及 PI3K 的信号通路的激活似乎是导致 McNtcp 耐受的主要机制。 24 细胞与牛磺酸结合的胆汁酸。
Background: The liver-derived McNtcp. 24 cells transport bile acids and show distinctive responses to the two classes of conjugated bile acids. Whereas taurine-conjugated bile acids are non-toxic, glycine-conjugated bile acids efficiently induce apoptosis. The aim of this study was to determine if the differential sensitivity is limited to cells that normally transport bile acids and if bile acid binding proteins could reduce bile acid-mediated apoptosis. The apical sodium/bile acid cotransporter (asbt) was expressed in Chinese hamster ovary (CHO) cells to establish active bile acid transport in a non-liver-derived cell model (CHO. asbt). A high-affinity bile acid binder was expressed in McNtcp. 24 cells.Results: The tolerance of McNtcp. 24 cells to taurine-conjugated bile acids was associated with the stimulation of phosphatidylinositol 3-kinase (PI3K) activity. Treatment of CHO. asbt cells with taurine-and glycine-conjugated bile acids resulted in apoptosis. Unlike in McNtcp. 24 cells, PI3K activity was not increased in CHO. asbt cells treated with taurine-conjugated bile acids. High level expression of a bile acid binder did not attenuate bile acid-induced cytotoxicity in McNtcp. 24 cells.Conclusion: The data suggest that McNtcp. 24 cells possess a mechanism that can elaborate distinctive responses to the different classes of bile acids. Additionally, activation of a signaling pathway involving PI3K appears to be the dominant mechanism responsible for the tolerance of McNtcp. 24 cells to taurine-conjugated bile acids.