硫氧还蛋白相互作用蛋白与卵母细胞葡萄糖代谢关系的研究进展

doi:10.3864/j.issn.0578-1752.2015.S.009

摘要/Abstract

摘要： 硫氧还蛋白相互作用蛋白（thioredoxin-interacting protein, TXNIP）属于硫氧还蛋白（thioredoxin，Trx）超家族成员，是α-抑制蛋白家族中唯一能够与Trx结合并对Trx进行负调控的蛋白，通过与凋亡信号调节激酶1（apoptosis signal-regulating kinase 1,ASK1）竞争性结合Trx而抑制Trx系统功能，在诱导细胞凋亡和调节胞内氧化还原状态过程中发挥重要的作用。TXNIP也是参与葡萄糖代谢的一个关键调控因子，在高浓度葡萄糖的诱导下，通过招募碳水化合物应答元件结合蛋白（carbohydrate response element-binding protein, ChREBP）和转录因子MondoA：Mlx到TXNIP的启动子，引起TXNIP的表达。组蛋白去乙酰化酶1（histone deacetylase 1，HDAC1）、核因子Y（nuclear factor Y，NF-Y）和转录因子FOXO1等都能调控TXNIP的转录。TXNIP还能通过抑制周期蛋白依赖性激酶的活性对抗细胞增殖。研究发现，TXNIP通过诱导胰岛β细胞的凋亡，抑制胰岛素信号转导途径，促进糖尿病及其并发症的发生。临床数据表明，糖尿病引起的高血糖严重影响卵母细胞的代谢和质量。葡萄糖作为许多细胞功能的作用底物，能够调节卵母细胞的减数分裂进程。在卵母细胞成熟过程中，葡萄糖通过多条代谢途径进行代谢，包括糖酵解途径、磷酸戊糖途径、己糖胺生物合成途径和多元醇途径。近年的研究揭示TXNIP缺失使大部分卵母细胞阻滞在MI期，破坏了卵母细胞内的肌动蛋白网络，卵母细胞的葡萄糖摄取和乳酸生成量增加，说明TXNIP是卵母细胞葡萄糖代谢的一个关键调控分子。综上所述，TXNIP与卵母细胞的葡萄糖代谢之间可能存在复杂的调控关系。将TXNIP用作卵母细胞葡萄糖代谢调控的靶位点进行深入研究，将为生殖细胞代谢异常提供重要理论参考，具有重要的应用前景。因此，文章对TXNIP的结构及调控机制、卵母细胞葡萄糖代谢途径、及TXNIP与卵母细胞葡萄糖代谢的关系进行了综述。

关键词: TXNIP, 卵母细胞, 葡萄糖, 代谢

Abstract: Thioredoxin-interacting protein (TXNIP) is a member of the thioredoxin (Trx) super family of proteins, which is the only α-arrestin family member that binds to and negatively regulates Trx. TXNIP can inhibit the function of Trx system by binding Trx, and act as a competitive inhibitor to remove Trx from apoptosis signal-regulating kinase 1 (ASK1). TXNIP is closely related to the cellular reduction-oxidation (redox) state and plays an important role in cell apoptosis. TXNIP is a critical regulator of glucose metabolism. High glucose recruits carbohydrate response element-binding protein (ChREBP) and the transcription factor MondoA:Mlx to the TXNIP promoter and mediates glucose-induced TXNIP expression. Histone deacetylase 1(HDAC1), nuclear factor Y (NF-Y) and the forkhead boxO1 transcription factor (FOXO1) have been reported to regulate the transcription of TXNIP. TXNIP can also inhibit cell proliferation by repressing cyclin-dependent kinase activity. Some studies have found that elevated TXNIP levels induce beta cell apoptosis and inhibit insulin signaling pathway, then promote the occurrence of diabetes and the associated medical comorbidities. Clinical data suggest that hyperglycemia induced by diabetes seriously affects metabolic activity and quality in oocytes. Glucose is the substrate for many cellular functions that can regulate the process of meiosis, and is metabolised by glycolysis pathway, the pentose phosphate pathway, the hexosamine biosynthesis pathway and the polyol pathway. Recent studies have revealed that upon specific depletion of TXNIP, most of oocytes were arrested at metaphate I (MI) stage, which exhibited disturbed actin networking and upregulated glucose uptake and lactate production, indicating that TXNIP is an important regulator of glucose metabolism in oocytes. In summary, it may exist complex regulatory relationships between TXNIP and glucose metabolism in oocytes. TXNIP may be a critical target mediating glucose metabolism in oocytes, and further study will provide important theoretical reference for abnormal metabolic studies. Hence, the structure and regulatory mechanism of TNXIP, pathways of glucose metabolism in oocytes and the relationship between TXNIP and glucose metabolism in oocytes are reviewed in this paper.

Key words: TXNIP, oocyte, glucose, metabolism

庞云渭，孙业清，杜卫华，郝海生，赵学明，王栋，朱化彬. 硫氧还蛋白相互作用蛋白与卵母细胞葡萄糖代谢关系的研究进展[J]. 中国农业科学, 2015, 48(S): 75-85.

PANG Yun-wei, SUN Ye-qing, DU Wei-hua, HAO Hai-sheng, ZHAO Xue-ming, WANG Dong, ZHU Hua-bin. Research Advance on the Relationship Between Thioredoxin- Interacting Protein and Glucose Metabolism in Oocytes[J]. Scientia Agricultura Sinica, 2015, 48(S): 75-85.

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