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山东大学学报 (医学版) ›› 2019, Vol. 57 ›› Issue (2): 93-98.doi: 10.6040/j.issn.1671-7554.0.2018.1460

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腺苷酸依赖的蛋白激酶在子宫腺肌症中的表达及其作用

黄毓菲1,杨阳1,邵倩倩2,邓晓惠1,晁岚1   

  1. 1. 山东大学齐鲁医院妇产科不孕不育诊疗中心, 山东 济南 250012;2.山东大学齐鲁医院心血管重构与〓功能研究 中华人民共和国教育部与卫生部重点实验室, 临床基础研究所, 山东 济南 250012
  • 发布日期:2022-09-27
  • 通讯作者: 晁岚. E-mail:qlszcl@163.com
  • 基金资助:
    国家自然科学基金(81571511、81701528、81370711)

Expression and role of adenosine monophosphate dependent protein kinase in adenomyosis

HUANG Yufei1, YANG Yang1, SHAO Qianqian2, DENG Xiaohui1, CHAO Lan1   

  1. 1. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    2. Institute of Basic Medical Sciences, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Published:2022-09-27

摘要: 目的 通过检测腺苷酸依赖的蛋白激酶(AMPK)在子宫腺肌症患者在位子宫内膜组织中的表达和定位,探讨AMPK在子宫腺肌症发病中的作用。 方法 免疫组织化学染色法检测子宫腺肌症患者在位子宫内膜组织(20例)和对照组正常子宫内膜(20例)中AMPK的表达情况;Real-time PCR检测子宫腺肌症患者在位子宫内膜组织和对照组正常子宫内膜中AMPK、M2型丙酮酸激酶(PKM2)mRNA表达水平;Western blotting检测子宫腺肌症患者在位子宫内膜组织和对照组正常子宫内膜中AMPK、PKM2蛋白表达水平。 结果 AMPK主要在子宫腺肌症患者在位子宫内膜组织和对照组正常子宫内膜中的腺上皮细胞质中表达,免疫组化结果显示子宫腺肌症患者在位子宫内膜腺上皮细胞中AMPK表达在分泌期和增殖期均高于正常子宫内膜(P<0.001),而对照组、实验组相应的增殖期和分泌期中AMPK表达差异无统计学意义(P>0.05)。子宫腺肌症患者在位内膜组织中AMPK、PKM2 mRNA表达水平和蛋白表达水平均高于正常子宫内膜,差异有统计学意义(P<0.001),而对照组、实验组相应的增殖期和分泌期中AMPK、PKM2 mRNA表达水平和蛋白表达水平差异无统计学意义(P>0.05)。 结论 AMPK可能通过促进糖酵解代谢在子宫腺肌症的发生发展中发挥作用。

关键词: 子宫腺肌症, 子宫内膜, 腺苷酸依赖的蛋白激酶, M2型丙酮酸激酶, 信号通路

Abstract: Objective To explore the role of adenosine monophosphate dependent protein kinase(AMPK)in the pathogenesis of adenomyosis by investigating its expression and localization in the eutopic endometrial tissues in adenomyosis. Methods The localizations of AMPK in eutopic adenomyosis endometrium(20 cases)and normal endometrium(20 cases)were detected with immunohistochemistry. The mRNA and protein expressions of AMPK and M2 pyruvate kinase(PKM2)were determined with Real-time PCR and Western blotting, respectively. Results AMPK was mainly expressed in the glandular epithelial cytoplasm in normal endometrium and eutopic adenomyosis endometrium. Immunohistochemistry showed that AMPK expression was higher in eutopic adenomyosis endometrium than in normal endometrium either in the secretory or proliferative phases(P<0.001), while there were no statistical differences in the expression of AMPK in the proliferative phase and secretory phase of each group(all P>0.05). The mRNA and protein expressions of AMPK and PKM2 were higher in eutopic adenomyosis endometrium than in normal endometrium(P<0.001), while there were no statistical differences in the mRNA and protein expressions of adenosine monophosphate and PKM2 山 东 大 学 学 报 (医 学 版)57卷2期 -黄毓菲,等.腺苷酸依赖的蛋白激酶在子宫腺肌症中的表达及其作用 \=-in the proliferative phase and secretory phase of each group(all P>0.05). Conclusion AMPK promotes glycolysis and plays an important role in the genesis and development of adenomyosis.

Key words: Adenomyosis, Endometrium, Adenosine monophosphate-dependent protein kinase, M2 pyruvate kinase, Signaling pathway

中图分类号: 

  • R711.71
[1] Harada T, Khine YM, Kaponis A, et al. The impact of adenomyosis on womens fertility [J]. Obstet Gynecol Surv, 2016, 71(9): 557-568.
[2] Pontis A, DAlterio MN, Pirarba S, et al. Adenomyosis: a systematic review of medical treatment [J]. Gynecol Endocrinol, 2016, 32(9): 696-700.
[3] 熊小琴, 布占红, 朱虹,等. 部分与全部子宫内膜电切术治疗子宫腺肌症临床疗效观察[J]. 中国研究型医院, 2018, 5(5): 41-43. XIONG Xiaoqin, BU Zhanhong, ZHU Hong, et al. Clinical efficacy of partial and total endometrial resection for adenomyosis[J]. Journal of Chinese Research Hospitals, 2018, 5(5): 41-43.
[4] Vannuccini S, Luisi S, Tosti C, et al. Role of medical therapy in the management of uterine adenomyosis [J]. Fertil Steril, 2018, 109(3): 398-405.
[5] Vannuccini S, Tosti C, Carmona F, et al. Pathogenesis of adenomyosis: an update on molecular mechanisms [J]. Reprod Biomed Online, 2017, 35(5): 592-601.
[6] Jeon SM. Regulation and function of AMPK in physiology and diseases[J]. Exp Mol Med, 2016, 48(7): e245. doi:10.1038/emm.2016.81.
[7] Villanueva-Paz M, Cotán D, Garrido-Maraver J, et al. AMPK regulation of cell growth, apoptosis, autophagy, and bioenergetics[J]. Exp Suppl, 2016, 107: 45-71. doi:10.1007/978-3-319-43589-3_3.
[8] Kim N, Lee JO, Lee HJ, et al. AMPK, a metabolic sensor, is involved in isoeugenol-induced glucose uptake in muscle cells[J]. J Endocrinol, 2016, 228(2): 105-114.
[9] Huang X, Li X, Xie X, et al. High expressions of LDHA and AMPK as prognostic biomarkers for breast cancer [J]. Breast, 2016, 30: 39-46. doi:10.1016/j.breast.2016.08.014.
[10] Younes G, Tulandi T. Effects of adenomyosis on in vitro fertilization treatment outcomes: a meta-analysis [J]. Fertil Steril, 2017, 108(3): 483-490.
[11] Dueholm M. Uterine adenomyosis and infertility, review of reproductive outcome after in vitro fertilization and surgery[J]. Acta Obstet Gynecol Scand, 2017, 96(6): 715-726.
[12] Kishi Y, Shimada K, Fujii T, et al. Phenotypic characterization of adenomyosis occurring at the inner and outer myometrium[J]. PLoS One, 2017, 12(12): e0189522. doi:10.1371/journal.pone.0189522.
[13] Ha J, Guan KL, Kim J. AMPK and autophagy in glucose/glycogen metabolism[J]. Mol Aspects Med, 2015, 46: 46-62. doi:10.1016/j.mam.2015.08.002.
[14] Cokorinos EC, Delmore J, Reyes AR, et al. Activation of skeletal muscle AMPK promotes glucose disposal and glucose lowering in non-human primates and mice [J]. Cell Metab, 2017, 25(5): 1147-1159.e10. doi:10.1016/j.cmet.2017.04.010.
[15] Possik E, Ajisebutu A, Manteghi S, et al. FLCN and AMPK confer resistance to hyperosmotic stress via remodeling of glycogen stores[J]. PLoS Genet, 2015, 11(10): e1005520. doi:10.1371/journal.pgen.1005520.
[16] San-Millán I, Brooks GA. Reexamining cancer metabolism: lactate production for carcinogenesis could be the purpose and explanation of the Warburg Effect [J]. Carcinogenesis, 2017, 38(2): 119-133.
[17] Tekade RK, Sun X. The Warburg effect and glucose-derived cancer theranostics [J]. Drug Discov Today, 2017, 22(11): 1637-1653.
[18] Faubert B, Boily G, Izreig S, et al. AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo [J]. Cell Metab, 2013, 17(1): 113-124.
[19] Wiese EK, Hitosugi T. Tyrosine Kinase Signaling in Cancer Metabolism: PKM2 Paradox in the Warburg Effect [J]. Front Cell Dev Biol, 2018, 6: 79. doi:10.3389/fcell.2018.00079.
[20] Zheng X, Zhou Y, Chen W, et al. Ginsenoside 20(S)-Rg3 prevents PKM2-targeting mir-324-5p from H19 sponging to antagonize the Warburg Effect in ovarian cancer cells [J]. Cell Physiol Biochem, 2018, 51(3): 1340-1353.
[21] Zhou L, Jiang S, Fu Q, et al. FASN, ErbB2-mediated glycolysis is required for breast cancer cell migration [J]. Oncol Rep, 2016, 35(5): 2715-2722.
[22] Yan XL, Zhang XB, Ao R, et al. Effects of shRNA-mediated silencing of PKM2 gene on aerobic glycolysis, cell migration, cell invasion, and apoptosis in colorectal cancer cells [J]. J Cell Biochem, 2017, 118(12): 4792-4803.
[23] Chakraborty PK, Mustafi SB, Xiong X, et al. MICU1 drives glycolysis and chemoresistance in ovarian cancer [J]. Nat Commun, 2017, 8: 14634. doi:10.1038/ncomms14634.
[24] Jin L, Chun J, Pan C, et al. Phosphorylation-mediated activation of LDHA promotes cancer cell invasion and tumour metastasis [J]. Oncogene, 2017, 36(27): 3797-3806.
[25] Li L, Zhu L, Hao B, et al. iNOS-derived nitric oxide promotes glycolysis by inducing pyruvate kinase M2 nuclear translocation in ovarian cancer [J]. Oncotarget, 2017, 8(20): 33047-33063.
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