Effects of taurine depletion on human placental syncytiotrophoblast renewal and susceptibility to oxidative stress.

Effects of taurine depletion on human placental syncytiotrophoblast renewal and susceptibility to oxidative stress.
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DOI:
10.1007/978-3-319-15126-7_6
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发表时间:
2015
影响因子:
--
通讯作者:
Greenwood, Susan L.
Greenwood, Susan L.
中科院分区:
医学4区
文献类型:
--
作者:
Desforges, Michelle;Whittaker, Hannah;Farmer, Etaoin;Sibley, Colin P.;Greenwood, Susan L.

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牛磺酸在人类妊娠中是条件性必需的,因为胎儿组织不表达生物合成酶。胎儿和胎盘对牛磺酸的需求必须通过牛磺酸转运蛋白(TauT)从母体血液中充分摄取到胎盘的转运上皮细胞合胞体滋养层(STB)中来满足。STB TauT活性在妊娠并发症先兆子痫(PE)中降低。这种病症与胎儿生长受限(FGR)和胎盘病理学相关,包括异常STB更新、线粒体功能障碍和氧化应激升高。在非胎盘细胞中,细胞内牛磺酸具有细胞保护作用,并调节增殖、分化和凋亡;这是STB更新中的关键事件。在此,我们测试了STB牛磺酸缺乏通过损害线粒体功能而损害更新并增加对氧化应激的易感性的假设。在存在10 mM β-丙氨酸的情况下,在培养7天以上的胎盘绒毛外植体中评估STB更新和对氧化应激的易感性,以竞争性地抑制牛磺酸摄取。在外植体培养过程中,STB脱落,然后通过类似于体内的过程再生。免疫组化显示β-丙氨酸显著降低了再生STB的绒毛比例。在STB的外植体处理与1 mM H2 O2(诱导剂的氧化应激),在细胞核和细胞质(线粒体DNA)中的氧化DNA损伤显着高于TauT抑制。BeWo细胞中牛磺酸耗竭诱导线粒体肿胀,线粒体复合物V亚基表达减少,氧化应激增加,表明线粒体功能障碍。这些数据表明,牛磺酸对于维持STB更新和保护免受氧化应激引起的损伤是重要的,可能通过涉及线粒体功能调节的机制。
Taurine is conditionally essential in human pregnancy as fetal tissues do not express the biosynthetic enzyme. Taurine demand by both fetus and placenta must be met by sufficient uptake from maternal blood into syncytiotrophoblast (STB), the transport epithelium of the placenta, via the taurine transporter (TauT). STB TauT activity is reduced in the pregnancy complication pre-eclampsia (PE). This condition is associated with fetal growth restriction (FGR) and placental pathology comprising abnormal STB renewal, mitochondrial dysfunction, and elevated oxidative stress. In non-placental cells intracellular taurine is cytoprotective and regulates proliferation, differentiation, and apoptosis; key events in STB renewal. Here we test the hypothesis that STB taurine deficiency impairs renewal and increases susceptibility to oxidative stress by compromising mitochondrial function.STB renewal and susceptibility to oxidative stress was assessed in placental villous explants cultured over 7 days in the presence of 10 mM β-alanine to competitively inhibit taurine uptake. During explant culture, STB sheds and thereafter is regenerated by processes resembling thosein vivo. Immunohistochemical techniques demonstrated β-alanine significantly reduced the proportion of villi with regenerated STB. In STB of explants treated with 1 mM H2O2(inducer of oxidative stress), oxidative DNA damage in nuclei and cytoplasm (mitochondrial DNA) was significantly higher following TauT inhibition. Taurine depletion in BeWo cells induced mitochondrial swelling, reduced mitochondrial complex V subunit expression and increased oxidative stress, indicating mitochondrial dysfunction. These data suggest that taurine is important for maintaining STB renewal and protecting against damage caused by oxidative stress, possibly via a mechanism involving regulation of mitochondrial function.
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DOI: 10.1007/978-1-4614-6093-0_17
发表时间: 2013-01-01
期刊: TAURINE 8, VOL 2: NUTRITION AND METABOLISM, PROTECTIVE ROLE, AND ROLE IN REPRODUCTION, DEVELOPMENT, AND DIFFERENTIATION
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