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山东大学学报 (医学版) ›› 2020, Vol. 58 ›› Issue (4): 84-89.doi: 10.6040/j.issn.1671-7554.0.2019.1388

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核糖体蛋白S6激酶2沉默在乙醇诱导的心肌胰岛素抵抗中的作用

徐红照1,郝宗山2, 沈德嫱3,李朝苹4,陈立勇4   

  1. 1. 山东大学公共卫生学院卫生毒理与营养学系, 山东 济南 250012;2. 山东大学附属山东省耳鼻喉医院, 山东 济南 250021;3. 徐州医科大学附属连云港医院临床营养科, 江苏 连云港 222002;4. 山东大学附属省立医院营养科, 山东 济南250021
  • 发布日期:2022-09-27
  • 通讯作者: 陈立勇. E-mail:chenle73@sina.com

Ribosomal protein S6 kinase 2 silencing in ethanol-induced myocardial insulin resistance

XU Hongzhao1, HAO Zongshan2, SHEN Deqiang3, LI Zhaoping4, CHEN Liyong4   

  1. 1. Department of Toxicology and Nutrition, School of Public Health, Shandong University, Jinan 250012, Shandong, China;
    2. Shandong Provincial ENT Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
    3. Department of Clinical Nutrition, Lianyungang Hospital Affiliated to Xuzhou Medical University, Lianyungang 222002, Jiangsu, China;
    4. Department of Nutrition, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
  • Published:2022-09-27

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摘要： 目的 探讨核糖体蛋白S6激酶2(S6K2)沉默在乙醇诱导的心肌胰岛素抵抗中的作用。 方法 采用荧光标记2-脱氧葡萄糖(2-NDBG)摄取实验及葡萄糖氧化酶法检测在100 mmol乙醇刺激下,沉默S6K2前后心肌细胞H9c2糖摄取能力。采用Western blotting法检测乙醇处理及病毒转染前后S6K2蛋白表达量及胰岛素受体底物 1(p-IRS-1)磷酸化情况。采用q-PCR及Western blotting法检测慢病毒转染后S6K2的沉默情况。 结果 乙醇刺激降低了心肌细胞H9c2葡萄糖摄取,2-NDBG平均荧光强度降低46.5%(P=0.016),同时p-IRS-1(Ser)蛋白表达量提高14.4%(P=0.024),S6K2在mRNA及蛋白水平表达分别上调16.8%和23.5%(P=0.009,P=0.029)。S6K2沉默后,乙醇刺激对H9c2心肌细胞糖摄取及p-IRS-1(Ser)的表达差异无统计学意义(P=0.665,P=0.740)。 结论 乙醇刺激导致心肌细胞糖摄取障碍,诱导胰岛素抵抗,S6K2沉默能够有效改善乙醇诱导的心肌细胞葡萄糖摄取障碍及胰岛素抵抗现象。

关键词: 乙醇, 心肌, 胰岛素抵抗, H9c2心肌细胞, 核糖体蛋白S6激酶2

Abstract: Objective To explore the role of ribosomal protein S6 kinase 2(S6K2)in ethanol-induced myocardial insulin resistance. Methods The glucose uptake capacity of H9c2 cells after 100 mmol ethanol stimulation and lentivirus transfection was detected with fluorescence labeling 2-deoxy-2-［(7-nitro-2,1,3-benzoxadiazol-4-yl)amino］-D-glucose(2-NDBG)intake test and glucose oxidase. The expression of S6K2 and phosphorylation of insulin receptor substrate 1(p-IRS-1)were determined with Western blotting. The silencing of S6K2 after lentivirus transfection was detected with real time PCR and Western blotting. Results Ethanol exposure impaired glucose uptake in H9c2 cells. The mean fluorescence intensity of 2-NDBG decreased by 46.5%(P=0.016), the protein expression of p-IRS-1(Ser)increased by 14.4%(P=0.024), and the mRNA and protein expressions of S6K2 increased by 16.8% and 23.5% respectively(P=0.009, P=0.029). After S6K2 silencing, the difference of glucose uptake and p-IRS-1(Ser)expression in ethanol-stimulated H9c2 cells had no statistics significance(P=0.665, P=0.740). Conclusion Ethanol exposure triggers glucose intolerance and insulin resistance in H9c2 cells, and S6K2 silencing can alleviate impaired glucose uptake and insulin sensitivity induced by ethanol.

Key words: Ethanol, Myocardium, Insulin resistance, H9c2 cardiomyocyte, Ribosomal protein S6 kinase 2

中图分类号: 

  • R542.2
[1] Mogos MF, Salemi JL, Phillips SA, et al. Contemporary appraisal of sex differences in prevalence, correlates, and outcomes of alcoholic cardiomyopathy [J]. Alcohol Alcohol, 2019, 54(4): 386-395.
[2] 张天懿, 高卫民, 曹志鹏, 等. 酒精性心肌病的研究进展及其法医学鉴定[J]. 法医学杂志, 2019, 35(6): 721-725. ZHANG Tianyi, GAO Weimin, CAO Zhipeng, et al. Research progress and forensic identification of alcoholic cardiomyopathy [J]. Journal of Forensic Medicine, 2019, 35(6): 721-725.
[3] Li SY, Ren J. Cardiac overexpression of alcohol dehydrogenase exacerbates chronic ethanol ingestion-induced myocardial dysfunction and hypertrophy: role of insulin signaling and ER stress [J]. J Mol Cell Cardiol, 2008, 44(6): 992-1001.
[4] Dinh W, Lankisch M, Nickl W, et al. Insulin resistance and glycemic abnormalities are associated with deterioration of left ventricular diastolic function: a cross-sectional study [J]. Cardiovasc Diabetol, 2010, 9: 63. doi:10.1186/1475-2840-9-63.
[5] Novo G, Pugliesi M, Visconti C, et al. Early subclinical ventricular dysfunction in patients with insulin resistance [J]. J Cardiovasc Med(Hagerstown), 2014, 15(2): 110-114.
[6] Lee-Fruman KK, Kuo CJ, Lippincott J, et al. Characterization of S6K2, a novel kinase homologous to S6K1 [J]. Oncogene, 1999, 18(36): 5108-5114.
[7] Fernández-Solà J. Cardiovascular risks and benefits of moderate and heavy alcohol consumption [J]. Nat Rev Cardiol, 2015, 12(10): 576-587.
[8] Day E, Rudd JHF. Alcohol use disorders and the heart [J]. Addiction, 2019, 114(9): 1670-1678.
[9] Fu F, Zhao K, Li J, et al. Direct evidence that myocardial insulin resistance following myocardial ischemia contributes to post-ischemic heart failure [J]. Sci Rep, 2016, 5: 17927. doi:10.1038/srep17927.
[10] Yazıcı D, Sezer H. Insulin resistance, obesity and lipotoxicity [J]. Adv Exp Med Biol, 2017, 960: 277-304. doi:10.1007/978-3-319-48382-5_12.
[11] Magnuson B, Ekim B, Fingar DC. Regulation and function of ribosomal protein S6 kinase(S6K)within mTOR signalling networks [J]. Biochem J, 2012, 441(1): 1-21.
[12] Goh ET, Pardo OE, Michael N, et al. Involvement of heterogeneous ribonucleoprotein F in the regulation of cell proliferation via the mammalian target of rapamycin/S6 kinase 2 pathway [J]. J Biol Chem, 2010, 285(22): 17065-17076.
[13] Foster KG, Fingar DC. Mammalian target of rapamycin(mTOR): conducting the cellular signaling symphony [J]. J Biol Chem, 2010, 285(19): 14071-14077.
[14] Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing [J]. Nat Rev Mol Cell Biol, 2011, 12(1): 21-35.
[15] 魏荣芳, 郭梦婕, 钱进军, 等. p70S6K1在结直肠癌中的作用及潜在分子机制(英文)[J]. 南京中医药大学学报, 2019, 35(5): 613-622.
[16] 王新, 于跃利. mTOR及其下游分子4EBP1和S6K1与结直肠腺癌关系的研究[J]. 系统医学, 2019, 4(3): 193-195.
[17] Filonenko VV, Tytarenko R, Azatjan SK, et al. Immunohistochemical analysis of S6K1 and S6K2 localization in human breast tumors [J]. Exp Oncol, 2004, 26(4): 294-299.
[18] 韩冰, 赵国军, 兰素伟, 等. 宫颈癌组织中S6K1和S6K2的表达及其临床意义[J]. 中国老年学杂志, 2017, 37(9): 2182-2185.
[19] Blouet C, Ono H, Schwartz GJ. Mediobasal hypothalamic p70S6 kinase 1 modulates the control of energy homeostasis [J]. Cell Metab, 2008, 8(6): 459-467.
[20] Pende M, Kozma SC, Jaquet M, et al. Hypoinsulinaemia, glucose intolerance and diminished-cell size in S6K1-deficient mice [J]. Nat, 2000, 408(6815): 994-997.
[21] Karlsson E, Magic I, Bostner J, et al. Revealing different roles of the mTOR-targets S6K1 and S6K2 in breast cancer by expression profiling and structural analysis [J]. PLoS ONE, 2015, 10(12): e0145013. doi: 10.1371/journal.pone.0145013.
[22] Lyzogubov V, Khozhaenko Y, Usenko V, et al. Immunohistochemical analysis of Ki-67, PCNA and S6K1/2 expression in human breast cancer [J]. Exp Oncol, 2005, 27(2): 141-144.
[23] Pardo OE, Seckl MJ. S6K2: The neglected S6 kinase family member [J]. Front in Oncol, 2013, 3: 191. doi: 10.3389/fonc.2013.00191.
[24] Sun Y, Luo M, Chang G, et al. Phosphorylation of Ser6 in hnRNPA1 by S6K2 regulates glucose metabolism and cell growth in colorectal cancer [J]. Oncol Lett, 2017, 14(6): 7323-7331.
[25] Sever N(·overI), Cengiz ?瘙塁ahin S. S6K2 promises an important therapeutic potential for cancer [J]. Future Oncol, 2019, 15(1): 95-102.
[26] Ismail HM, Myronova O, Tsuchiya Y, et al. Identification of the general transcription factor Yin Yang 1 as a novel and specific binding partner for S6 Kinase 2 [J]. Cell Signal, 2013, 25(5): 1054-1063.
[27] Miller WP, Ravi S, Martin TD, et al. Activation of the stress response kinase JNK(c-Jun N-terminal Kinase)attenuates insulin action in retina through a p70S6K1-dependent mechanism [J]. J Biol Chem, 2017, 292(5): 1591-1602.
[28] Chen J, Sun J, Prinz RA. Gingerenone A sensitizes the insulin receptor and increases glucose uptake by inhibiting the activity of p70 S6 kinase [J]. Mol Nutr Food Res, 2018, 62(23): e1800709. doi: 10.1002/mnfr.201800709.
[29] Cao Y, Sun W, Xu G. Fuzhu jiangtang granules combined with metformin reduces insulin resistance in skeletal muscle of diabetic rats via PI3K/Akt signaling [J]. Pharm Biol, 2019, 57(1): 660-668.
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