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次牛磺酸对氧化应激诱导的大鼠胎盘滋养层细胞毒性的保护作用。

Protective effect of hypotaurine against oxidative stress-induced cytotoxicity in rat placental trophoblasts.

作者信息

Nishimura T, Duereh M, Sugita Y, Yoshida Y, Higuchi K, Tomi M, Nakashima E

机构信息

Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.

Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan; School of Pharmaceutical Sciences, Teikyo University, Itabashi-ku, Tokyo 173-8605, Japan.

出版信息

Placenta. 2015 Jun;36(6):693-8. doi: 10.1016/j.placenta.2015.02.014. Epub 2015 Mar 6.

Abstract

INTRODUCTION

Hypotaurine is a precursor of taurine and an antioxidant, and is concentrated in fetal plasma compared to maternal plasma. Hypotaurine is significantly decreased in fetal plasma of ezrin (Vil2) knock-out mice, and fetuses show intrauterine growth retardation. The aim of this study was to characterize the mechanism through which cellular hypotaurine level is maintained in placental trophoblasts, and the effect of hypotaurine on oxidative stress induced by hydrogen peroxide (H2O2).

METHODS

Hypotaurine transfer from extracellular fluid and antioxidant effect of hypotaurine were analyzed in rat placental trophoblast TR-TBT 18d-1 cells.

RESULTS

We found that hypotaurine is concentrated into rat placental trophoblast TR-TBT 18d-1 cells, and the level of hypotaurine was markedly reduced by culture in medium supplemented with dialyzed fetal bovine serum (FBS) instead of normal FBS. The hypotaurine level recovered almost completely when hypotaurine was added to the culture medium, indicating that intracellular hypotaurine is predominantly supplied by transport across the plasma membrane from extracellular fluid rather than by biosynthesis. Hypotaurine showed a cytoprotective effect against H2O2-induced oxidative damage in TR-TBT 18d-1 cells. Hypotaurine treatment of TR-TBT 18d-1 cells increased antioxidant capacity against hydroxyl radical and peroxyl radical. The concentration of intracellular hydroxyl radical induced by H2O2 in TR-TBT 18d-1 cells was significantly reduced by hypotaurine treatment.

DISCUSSION

These results indicate that intracellular hypotaurine is mainly supplied to placental trophoblasts by transfer from extracellular fluid across the plasma membrane, and may play a role in cell protection by scavenging reactive oxygen species.

摘要

引言

次牛磺酸是牛磺酸的前体和一种抗氧化剂,与母体血浆相比,其在胎儿血浆中浓度较高。在埃兹蛋白(Vil2)基因敲除小鼠的胎儿血浆中,次牛磺酸显著减少,且胎儿出现宫内生长迟缓。本研究的目的是阐明胎盘滋养层细胞维持细胞内次牛磺酸水平的机制,以及次牛磺酸对过氧化氢(H2O2)诱导的氧化应激的影响。

方法

在大鼠胎盘滋养层TR-TBT 18d-1细胞中分析次牛磺酸从细胞外液的转运及其抗氧化作用。

结果

我们发现次牛磺酸在大鼠胎盘滋养层TR-TBT 18d-1细胞中富集,并且当在添加了透析胎牛血清(FBS)而非正常FBS的培养基中培养时,次牛磺酸水平显著降低。当向培养基中添加次牛磺酸时,次牛磺酸水平几乎完全恢复,这表明细胞内次牛磺酸主要通过从细胞外液跨质膜转运而非生物合成来供应。次牛磺酸对TR-TBT 18d-1细胞中H2O2诱导的氧化损伤具有细胞保护作用。用次牛磺酸处理TR-TBT 18d-1细胞可增加对羟自由基和过氧自由基的抗氧化能力。次牛磺酸处理显著降低了TR-TBT 18d-1细胞中由H2O2诱导的细胞内羟自由基浓度。

讨论

这些结果表明,细胞内次牛磺酸主要通过从细胞外液跨质膜转运供应给胎盘滋养层细胞,并且可能通过清除活性氧在细胞保护中发挥作用。

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