• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

人糖原合酶激酶3α磷酸化的调控及其与精子活力的相关性

Regulation of Phosphorylation of Glycogen Synthase Kinase 3α and the Correlation with Sperm Motility in Human.

作者信息

Park Seung Hyun, Kim Young-Pil, Lee Jeong Min, Park Dong-Wook, Seo Ju Tae, Gye Myung Chan

机构信息

Department of Life Science and Institute for Natural Sciences, Hanyang University, Seoul, Korea.

Graduate School of Global Pharmaceutical Industry and Clinical Pharmacy, Ajou University, Suwon, Korea.

出版信息

World J Mens Health. 2024 Apr;42(2):373-383. doi: 10.5534/wjmh.230004. Epub 2023 Aug 9.

DOI:10.5534/wjmh.230004
PMID:37635337
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10949033/
Abstract

PURPOSE

To unravel the mechanism regulating the phosphorylation of glycogen synthase kinase 3 (GSK3) and the correlation between the inhibitory phosphorylation of GSK3α and sperm motility in human.

MATERIALS AND METHODS

The phosphorylation and priming phosphorylated substrate-specific kinase activity of GSK3 were examined in human spermatozoa with various motility conditions.

RESULTS

In human spermatozoa, GSK3α/β was localized in the head, midpiece, and principal piece of tail and p-GSK3α(Ser21) was enriched in the midpiece. The ratio of p-GSK3α(Ser21)/GSK3α was positively coupled with normal sperm motility criteria of World Health Organization. In high-motility spermatozoa, p-GSK3α(Ser21) phosphotyrosine (p-Tyr) proteins but p-GSK3α(Tyr279) markedly increased together with decreased kinase activity of GSK3 after incubation in Ca containing medium. In high-motility spermatozoa, p-GSK3α(Ser21) levels were negatively coupled with kinase activity of GSK3, and which was deregulated in low-motility spermatozoa. In high-motility spermatozoa, 6-bromo-indirubin-3'-oxime, an inhibitor of kinase activity of GSK3 increased p-GSK3α(Ser21) and p-Tyr proteins. p-GSK3α(Ser21) and p-Tyr protein levels were decreased by inhibition of PKA and Akt. Calyculin A, a protein phosphatase-1/2A inhibitor, markedly increased the p-GSK3α(Ser21) and p-Tyr proteins, and significantly increased the motility of low-motility human spermatozoa.

CONCLUSIONS

Down regulation of kinase activity of GSK3α by inhibitory phosphorylation was positively coupled with human sperm motility, and which was regulated by Ca, PKA, Akt, and PP1. Small-molecule inhibitors of GSK3 and PP1 can be considered to potentiate human sperm motility.

摘要

目的

揭示调节糖原合酶激酶3（GSK3）磷酸化的机制以及人精子中GSK3α抑制性磷酸化与精子活力之间的相关性。

材料与方法

在具有不同活力状态的人精子中检测GSK3的磷酸化及引发磷酸化底物特异性激酶活性。

结果

在人精子中，GSK3α/β定位于头部、中段和尾部主段，p-GSK3α（Ser21）在中段富集。p-GSK3α（Ser21）/GSK3α的比值与世界卫生组织的正常精子活力标准呈正相关。在高活力精子中，在含钙培养基中孵育后，p-GSK3α（Ser21）磷酸酪氨酸（p-Tyr）蛋白以及p-GSK3α（Tyr279）显著增加，同时GSK3的激酶活性降低。在高活力精子中，p-GSK3α（Ser21）水平与GSK3的激酶活性呈负相关，而在低活力精子中这种相关性失调。在高活力精子中，GSK3激酶活性抑制剂6-溴靛玉红-3'-肟增加了p-GSK3α（Ser21）和p-Tyr蛋白。抑制PKA和Akt可降低p-GSK3α（Ser21）和p-Tyr蛋白水平。蛋白磷酸酶-1/2A抑制剂冈田酸显著增加了p-GSK3α（Ser21）和p-Tyr蛋白，并显著提高了低活力人精子的活力。

结论

抑制性磷酸化对GSK3α激酶活性的下调与人精子活力呈正相关，且受钙、PKA、Akt和PP1调节。GSK3和PP1的小分子抑制剂可被认为能增强人精子活力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/180b05b32cec/wjmh-42-373-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/d334ee140326/wjmh-42-373-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/99d6241ca37c/wjmh-42-373-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/5df4821c6d39/wjmh-42-373-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/30e0d8bd73a8/wjmh-42-373-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/3a76aa0ae09c/wjmh-42-373-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/6081c900e96e/wjmh-42-373-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/180b05b32cec/wjmh-42-373-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/d334ee140326/wjmh-42-373-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/99d6241ca37c/wjmh-42-373-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/5df4821c6d39/wjmh-42-373-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/30e0d8bd73a8/wjmh-42-373-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/3a76aa0ae09c/wjmh-42-373-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/6081c900e96e/wjmh-42-373-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ee/10949033/180b05b32cec/wjmh-42-373-g007.jpg

相似文献

1
Regulation of Phosphorylation of Glycogen Synthase Kinase 3α and the Correlation with Sperm Motility in Human.人糖原合酶激酶3α磷酸化的调控及其与精子活力的相关性
World J Mens Health. 2024 Apr;42(2):373-383. doi: 10.5534/wjmh.230004. Epub 2023 Aug 9.
2
Dibutyl phthalate disrupts glycogen synthase kinase 3α essential for sperm motility.邻苯二甲酸二丁酯通过破坏精子运动所必需的糖原合酶激酶 3α 发挥作用。
Ecotoxicol Environ Saf. 2024 Feb;271:115977. doi: 10.1016/j.ecoenv.2024.115977. Epub 2024 Jan 19.
3
Inhibition of mitochondrial cyclophilin D, a downstream target of glycogen synthase kinase 3α, improves sperm motility.抑制线粒体亲环素 D（糖原合成酶激酶 3α 的下游靶点）可改善精子活力。
Reprod Biol Endocrinol. 2024 Jan 22;22(1):15. doi: 10.1186/s12958-024-01186-x.
4
Glycogen Synthase Kinase-3 Isoform Variants and Their Inhibitory Phosphorylation in Human Testes and Spermatozoa.糖原合酶激酶-3亚型变体及其在人类睾丸和精子中的抑制性磷酸化
World J Mens Health. 2023 Jan;41(1):215-226. doi: 10.5534/wjmh.220108. Epub 2022 Aug 16.
5
Porcine sperm motility is regulated by serine phosphorylation of the glycogen synthase kinase-3alpha.猪精子活力受糖原合酶激酶-3α的丝氨酸磷酸化调控。
Reproduction. 2007 Sep;134(3):435-44. doi: 10.1530/REP-06-0388.
6
Differential role of bovine serum albumin and HCO3- in the regulation of GSK3 alpha during mouse sperm capacitation.牛血清白蛋白和 HCO3- 在调节小鼠精子获能过程中 GSK3α 中的差异作用。
Mol Hum Reprod. 2024 Feb 29;30(3). doi: 10.1093/molehr/gaae007.
7
Glycogen Synthase Kinase-3 Regulates Sperm Motility and Acrosome Reaction via Affecting Energy Metabolism in Goats.糖原合酶激酶-3通过影响山羊的能量代谢来调节精子活力和顶体反应。
Front Physiol. 2019 Jul 30;10:968. doi: 10.3389/fphys.2019.00968. eCollection 2019.
8
Isoform-specific requirement for GSK3α in sperm for male fertility.GSK3α 在精子中对雄性生育力的同工型特异性要求。
Biol Reprod. 2018 Aug 1;99(2):384-394. doi: 10.1093/biolre/ioy020.
9
Human sperm phosphoproteome reveals differential phosphoprotein signatures that regulate human sperm motility.人类精子磷酸蛋白质组揭示了调节人类精子运动的差异磷酸蛋白质特征。
J Proteomics. 2020 Mar 20;215:103654. doi: 10.1016/j.jprot.2020.103654. Epub 2020 Jan 20.
10
Cyclic AMP and glycogen synthase kinase 3 form a regulatory loop in spermatozoa.环腺苷酸和糖原合成酶激酶 3 在精子中形成一个调节环。
J Cell Physiol. 2018 Sep;233(9):7239-7252. doi: 10.1002/jcp.26557. Epub 2018 Mar 25.

引用本文的文献

1
Inhibition of mitochondrial cyclophilin D, a downstream target of glycogen synthase kinase 3α, improves sperm motility.抑制线粒体亲环素 D（糖原合成酶激酶 3α 的下游靶点）可改善精子活力。
Reprod Biol Endocrinol. 2024 Jan 22;22(1):15. doi: 10.1186/s12958-024-01186-x.

本文引用的文献

1
Glycogen Synthase Kinase-3 Isoform Variants and Their Inhibitory Phosphorylation in Human Testes and Spermatozoa.糖原合酶激酶-3亚型变体及其在人类睾丸和精子中的抑制性磷酸化
World J Mens Health. 2023 Jan;41(1):215-226. doi: 10.5534/wjmh.220108. Epub 2022 Aug 16.
2
Insulin Promotes Mitochondrial Respiration and Survival through PI3K/AKT/GSK3 Pathway in Human Embryonic Stem Cells.胰岛素通过 PI3K/AKT/GSK3 通路促进人胚胎干细胞的线粒体呼吸和存活。
Stem Cell Reports. 2020 Dec 8;15(6):1362-1376. doi: 10.1016/j.stemcr.2020.10.008. Epub 2020 Nov 12.
3
Molecular Basis of Human Sperm Capacitation.
人类精子获能的分子基础
Front Cell Dev Biol. 2018 Jul 27;6:72. doi: 10.3389/fcell.2018.00072. eCollection 2018.
4
The Key Roles of GSK-3β in Regulating Mitochondrial Activity.糖原合成酶激酶-3β在调节线粒体活性中的关键作用
Cell Physiol Biochem. 2017;44(4):1445-1459. doi: 10.1159/000485580. Epub 2017 Dec 1.
5
Heat Stress Reduces Sperm Motility via Activation of Glycogen Synthase Kinase-3α and Inhibition of Mitochondrial Protein Import.热应激通过激活糖原合酶激酶-3α和抑制线粒体蛋白导入来降低精子活力。
Front Physiol. 2017 Sep 22;8:718. doi: 10.3389/fphys.2017.00718. eCollection 2017.
6
Proliferation, survival and metabolism: the role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination.增殖、存活与代谢：PI3K/AKT/mTOR信号通路在多能性及细胞命运决定中的作用
Development. 2016 Sep 1;143(17):3050-60. doi: 10.1242/dev.137075.
7
Rapid Detection of Glycogen Synthase Kinase-3 Activity in Mouse Sperm Using Fluorescent Gel Shift Electrophoresis.利用荧光凝胶迁移电泳快速检测小鼠精子中的糖原合酶激酶-3活性
Sensors (Basel). 2016 Apr 16;16(4):551. doi: 10.3390/s16040551.
8
Counteracting Protein Kinase Activity in the Heart: The Multiple Roles of Protein Phosphatases.对抗心脏中的蛋白激酶活性：蛋白磷酸酶的多种作用。
Front Pharmacol. 2015 Nov 13;6:270. doi: 10.3389/fphar.2015.00270. eCollection 2015.
9
Post-transcriptional Wnt Signaling Governs Epididymal Sperm Maturation.转录后 Wnt 信号调控附睾精子成熟。
Cell. 2015 Nov 19;163(5):1225-1236. doi: 10.1016/j.cell.2015.10.029.
10
Sequential phosphorylation analysis using dye-tethered peptides and microfluidic isoelectric focusing electrophoresis.使用染料连接肽和微流控等电聚焦电泳进行顺序磷酸化分析。
Biosens Bioelectron. 2015 Nov 15;73:93-99. doi: 10.1016/j.bios.2015.05.047. Epub 2015 May 25.