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Taurine transport in human placental trophoblast is important for regulation of cell differentiation and survival

机译:人胎盘滋养细胞中的牛磺酸转运对于调节细胞分化和存活很重要

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摘要

The outer epithelial cell layer of human placenta, the syncytiotrophoblast, is a specialised terminally differentiated multinucleate tissue. It is generated and renewed from underlying cytotrophoblast cells that undergo proliferation, differentiation and fusion with syncytiotrophoblast. Acquisition of fresh cellular components is thought to be balanced by apoptosis and shedding of aged nuclei. This process of trophoblast cell turnover maintains a functional syncytiotrophoblast, capable of sufficient nutrient transfer from mother to foetus. Foetal growth restriction (FGR) is a pregnancy complication associated with aberrant trophoblast turnover and reduced activity of certain amino acid transporters, including the taurine transporter (TauT). Taurine is the most abundant amino acid in human placenta implying an important physiological role within this tissue. Unlike other amino acids, taurine is not incorporated into proteins and in non-placental cell types represents an important osmolyte involved in cell volume regulation, and is also cytoprotective. Here, we investigated the role of taurine in trophoblast turnover using RNA interference to deplete primary human trophoblast cells of TauT and reduce intracellular taurine content. Trophoblast differentiation was compromised in TauT-deficient cells, and susceptibility of these cells to an inflammatory cytokine that is elevated in FGR was increased, evidenced by elevated levels of apoptosis. These data suggest an important role for taurine in trophoblast turnover and cytoprotection.
机译:人胎盘的外上皮细胞层是合体滋养层细胞,是一种特殊的终末分化多核组织。它是由基础的滋养层细胞生成和更新的,这些细胞经过与合体滋养层细胞的增殖,分化和融合。认为新鲜细胞成分的获取与衰老细胞核的凋亡和脱落相平衡。滋养层细胞更新的过程保持功能性合体滋养层,能够将营养物质从母体转移到胎儿。胎儿生长受限(FGR)是一种妊娠并发症,与滋养层细胞更新异常和某些氨基酸转运蛋白(包括牛磺酸转运蛋白)的活性降低有关。牛磺酸是人胎盘中最丰富的氨基酸,暗示该组织内重要的生理作用。与其他氨基酸不同,牛磺酸不掺入蛋白质,在非胎盘细胞类型中,牛磺酸代表参与细胞体积调节的重要渗透压,并且具有细胞保护作用。在这里,我们研究了牛磺酸在滋养细胞更新中的作用,利用RNA干扰消耗了TauT的原代人类滋养细胞并减少了细胞内牛磺酸的含量。在TauT缺陷型细胞中,滋养层的分化受到损害,并且这些细胞对FGR升高的炎性细胞因子的敏感性增加,这由凋亡水平升高所证明。这些数据表明牛磺酸在滋养细胞更新和细胞保护中的重要作用。

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