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Thioredoxin-interacting protein regulates glucose metabolism and improves the intracellular redox state in bovine oocytes during in vitro maturation.

硫氧还蛋白相互作用蛋白调节葡萄糖代谢,改善牛卵母细胞体外成熟过程中的细胞内氧化还原状态。

  • 影响因子:3.89
  • DOI:10.1152/ajpendo.00057.2019
  • 作者列表:"Jiang X","Pang Y","Zhao S","Hao H","Zhao X","Du W","Wang Y","Zhu H
  • 发表时间:2020-03-01
Abstract

:The extent of glucose metabolism during oocyte maturation is closely related to oocyte developmental potential. Thioredoxin-interacting protein (TXNIP) is an α-arrestin family protein that negatively regulates glucose uptake into cells. However, little information is available regarding the function of TXNIP in bovine oocytes. Accordingly, the present study was performed to investigate the influence of TXNIP on glucose metabolism in bovine oocytes during in vitro maturation. Pharmacological inhibition of TXNIP by azaserine enhanced glucose uptake and imparted a specific metabolic effect on glycolysis and pentose phosphate pathway (PPP). RNA interference (RNAi) was adopted to further determine the biological significance of TXNIP in regulating glucose metabolism. The maturation rate and the developmental competence of TXNIP siRNA-treated oocytes were significantly improved. Knockdown of TXNIP in bovine oocytes significantly increased glycolysis by increasing the activities of phosphofructokinase (PFK), pyruvate kinase, and lactate dehydrogenase; pyruvate and lactate production; and intracellular ATP level, as well as mitochondrial activity. Furthermore, glucose metabolism through PPP was also enhanced by TXNIP depletion, as TXNIP siRNA treatment promoted glucose-6-phosphate dehydrogenase (G6PDH) activity and NADPH content, and helped maintain a high level of glutathione and a low level of reactive oxygen species within the oocytes. Further studies revealed that inhibition of TXNIP resulted increases in glucose transporter 1 (GLUT1) expression, as well as PFK1 platelet isoform (PFKP) and G6PDH mRNA levels. These results reveal that TXNIP depletion promotes oocyte maturation by enhancing both glycolysis and the PPP. During in vitro maturation of bovine oocytes, TXNIP serves as a key regulator of glucose uptake by controlling GLUT1 expression.

摘要

: 卵母细胞成熟过程中葡萄糖代谢的程度与卵母细胞发育潜能密切相关。硫氧还蛋白相互作用蛋白 (TXNIP) 是一种 α-抑制蛋白家族蛋白,其负性调节细胞对葡萄糖的摄取。然而,关于牛卵母细胞中TXNIP的功能的信息很少。因此,本研究旨在研究TXNIP对牛卵母细胞体外成熟过程中葡萄糖代谢的影响。阿扎丝氨酸对TXNIP的药理学抑制增强了葡萄糖摄取,并对糖酵解和磷酸戊糖途径 (PPP) 产生了特定的代谢作用。采用RNA干扰 (RNAi) 进一步确定TXNIP在调节糖代谢中的生物学意义。TXNIP siRNA处理的卵母细胞的成熟率和发育能力显著提高。牛卵母细胞中TXNIP的敲除通过增加磷酸果糖激酶 (PFK) 、丙酮酸激酶和乳酸脱氢酶的活性; 丙酮酸和乳酸产生; 和细胞内ATP水平以及线粒体活性来显著增加糖酵解。此外,通过PPP的葡萄糖代谢也通过TXNIP耗竭而增强,因为TXNIP siRNA处理促进葡萄糖-6-磷酸脱氢酶 (G6PDH) 活性和NADPH含量,并有助于维持卵母细胞内高水平的谷胱甘肽和低水平的活性氧。进一步的研究表明,TXNIP的抑制导致葡萄糖转运蛋白1 (GLUT1) 表达以及PFK1血小板同种型 (PFKP) 和G6PDH mRNA水平的增加。这些结果揭示了TXNIP耗竭通过增强糖酵解和PPP促进卵母细胞成熟。在牛卵母细胞的体外成熟过程中,TXNIP通过控制GLUT1表达而作为葡萄糖摄取的关键调节剂。

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影响因子:1.27
发表时间:2020-01-01
DOI:10.1111/ppc.12392
作者列表:["Safaei Nezhad A","Ebrahimi L","Vakili MM","Kharaghani R"]

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