我们的网站为什么显示成这样？

可能因为您的浏览器不支持样式，您可以更新您的浏览器到最新版本，以获取对此功能的支持，访问下面的网站，获取关于浏览器的信息：

|本期目录/Table of Contents|

抑制鞘氨醇激酶-2活性加重血管紧张素II诱导的心肌细胞肥大

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2018年第4期
页码:
373-377
栏目:
基础研究
出版日期:
2018-04-25

文章信息/Info

Title:
Pharmacological inhibition of sphingosine kinase-2 aggravates angiotensin II-induced cardiomyocyte hypertrophy
作者:
姬宇飞1; 陈希瑶2; 赵施皓1; 夏云龙1; 闫文俊1; 张富洋1; 陶 凌1
（第四军医大学西京医院：1.心血管内科，2.老年病科，陕西 西安 710032）
Author(s):
JI Yu-fei1;  CHEN Xi-yao2;  ZHAO Shi-hao1;  XIA Yun-long1;  YAN Wen-jun1 ZHANG Fu-yang1;  TAO Ling1
(1.Department of Cardiology, 2.Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
鞘氨醇激酶-2; 1-磷酸鞘氨醇; 血管紧张素II; 心肌细胞; 肥大
Keywords:
sphingosine kinase-2;  sphingosine 1-phosphate;  angiotensin II;  cardiomyocyte;  hypertrophy
分类号:
R741
DOI:
-
文献标识码:
A
摘要:
目的 本实验旨在明确鞘氨醇激酶（sphingosine kinase，SphK）2在血管紧张素（angiotensin，Ang）II诱导的心肌细胞肥大中的作用。方法 分离并体外培养SD乳鼠心肌细胞。给予AngII（10 μmol/L）处理24h诱导心肌细胞肥大。AngII刺激时分别给予溶媒或SphK2特异性抑制剂ABC294640（1 μmol/L）共处理。采用蛋白免疫印迹法检测心肌细胞SphK2蛋白表达。采用酶联免疫吸附试验（enzyme-linked immunosorbant assay，ELISA）检测心肌细胞细胞核1-磷酸鞘氨醇（sphingosine 1-phosphate，S1P）水平。采用结晶紫染色观察AngII诱导的心肌细胞肥大程度。采用实时定量聚合酶链式反应（real time-polymerase chain reaction,RT-PCR）检测心肌细胞肥大标志基因心房钠尿肽（atrial natriuretic peptide，ANP）、脑钠尿肽（brain natriuretic peptide，BNP）和β-肌球蛋白重链（β-myosin heavy chain，β-MHC）mRNA表达水平。结果 与对照组比较，AngII处理上调心肌细胞SphK2蛋白表达和S1P浓度（均P<0.05），并增加心肌细胞横截面积与ANP、BNP和β-MHC mRNA表达水平（均P<0.05）。与溶媒组比较，ABC294640处理显著降低了心肌细胞核S1P浓度，并进一步增加了AngII处理后的心肌细胞横截面积和肥大标志基因mRNA表达水平（均P<0.05）。结论 抑制SphK2活性加重AngII诱导的心肌细胞肥大。SphK2有可能成为治疗病理性心肌肥大的新靶点。
Abstract:
AIM The present study aimed to determine the role of sphingosine kinase-2 (SphK2) in angiotensin-II (AngII)-induced cardiomyocyte hypertrophy. METHODS Cardiomyocytes were isolated from Sprague Dawley rats and were cultured in vitro. Then, cardiomyocytes were exposed to AngII (10 μmol/L) for 24 hours. The expression of SphK2 was determined by Western blot and nuclear S1P abundance was analyzed by enzyme-linked immunosorbant assay (ELISA). After vehicle or ABC294640 (1 μmol/L) co-treatment, AngII-induced cardiomyocyte hypertrophy was assayed by crystal violet staining. The mRNA expression levels of hypertrophy marker genes, including artial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC), were determined by real-time polymerase chain reaction (RT-PCR). RESULTS The AngII treatment promoted cardiomyocyte hypertrophy and upregulated expression of hypertrophy marker genes. ABC294640 treatment significantly reduced nuclear S1P abundance in the cardiomyocyte. Notably, compared with the vehicle group, ABC294640 aggravated AngII-induced cardiomyocyte hypertrophy, as evidenced by increased cardiomyocyte size and expression of hypertrophy marker genes. CONCLUSION Inhibition of SphK2 exacerbates AngII-induced cardiomyocyte hypertrophy. SphK2 may be a potential therapeutic target for the prevention and treatment of pathological cardiac hypertrophy.

参考文献/References

[1]Cannon B.Cardiovascular disease:Biochemistry to behaviour[J].Nature,2013,493(7434):S2-S3.

[2]Opie LH,Commerford PJ,Gersh BJ,et al.Controversies in ventricular remodelling[J].Lancet,2006,367(9507):356-367.

[3]Shah AM,Shin SH,Takeuchi M,et al.Left ventricular systolic and diastolic function,remodelling,and clinical outcomes among patients with diabetes following myocardial infarction and the influence of direct renin inhibition with aliskiren[J].Eur J Heart Fail,2012,14(2):185-192.

[4]Roman MJ,Ganau A,Saba PS,et al.Left ventricular hypertrophy,arterial compliance,and aging[J].Adv Exp Med Biol,1997,432:13-22.

[5]Tamura T,Said S,Harris J,et al.Reverse remodeling of cardiac myocyte hypertrophy in hypertension and failure by targeting of the renin-angiotensin system[J].Circulation,2000,102(2):253-259.

[6]Maceyka M,Harikumar KB,Milstien S,et al.Sphingosine-1-phosphate signaling and its role in disease[J].Trends Cell Biol,2012,22(1):50-60.

[7]Alemany R,van Koppen CJ,Danneberg K,et al.Regulation and functional roles of sphingosine kinases[J].Naunyn Schmiedebergs Arch Pharmacol,2007,374(5-6):413-428.

[8]Olivera A,Spiegel S.Sphingosine kinase:a mediator of vital cellular functions[J].Prostaglandins Other Lipid Mediat,2001,64(1-4):123-134.

[9]Hait NC,Allegood J,Maceyka M,et al.Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate[J].Science,2009,325(5945):1254-1257.

[10]Maceyka M,Sankala H,Hait NC,et al.SphK1 and SphK2,sphingosine kinase isoenzymes with opposing functions in sphingolipid metabolism[J].J Biol Chem,2005,280(44):37118-37129.

[11]Taha TA,Kitatani K,El-Alwani M,et al.Loss of sphingosine kinase-1 activates the intrinsic pathway of programmed cell death:modulation of sphingolipid levels and the induction of apoptosis[J].FASEB J,2006,20(3):482-484.

[12]Waeber C,Walther T.Sphingosine-1-phosphate as a potential target for the treatment of myocardial infarction[J].Circ J,2014,78(4): 795-802.

[13]Means CK,Xiao CY,Li Z,et al.Sphingosine 1-phosphate S1P2 and S1P3 receptor-mediated Akt activation protects against in vivo myocardial ischemia-reperfusion injury[J].Am J Physiol Heart Circ Physiol,2007,292(6):H2944-H2951.

[14]Means CK,Brown JH. Sphingosine-1-phosphate receptor signalling in the heart[J].Cardiovasc Res,2009,82(2):193-200.

[15]Spijkers LJ,Alewijnse AE,Peters SL.FTY720(fingolimod)increases vascular tone and blood pressure in spontaneously hypertensive rats via inhibition of sphingosine kinase[J].Br J Pharmacol,2012,166(4):1411-1418.

[16]Zhang F,Xia Y,Yan W,et al.Sphingosine 1-phosphate signaling contributes to cardiac inflammation,dysfunction,and remodeling following myocardial infarction[J].Am J Physiol Heart Circ Physiol,2016,310(2):H250-H261.

[17]Gellings Lowe N,Swaney JS,Moreno KM,et al.Sphingosine-1-phosphate and sphingosine kinase are critical for transforming growth factor-beta-stimulated collagen production by cardiac fibroblasts[J].Cardiovasc Res,2009,82(2):303-312.

[18]Gerdes AM,Capasso JM.Structural remodeling and mechanical dysfunction of cardiac myocytes in heart failure[J].J Mol Cell Cardiol,1995,27(3):849-856.

[19]Gomez L,Paillard M,Price M,et al.A novel role for mitochondrial sphingosine-1-phosphate produced by sphingosine kinase-2 in PTP-mediated cell survival during cardioprotection[J].Basic Res Cardiol,2011,106(6):1341-1353.

备注/Memo

备注/Memo:
收稿日期：2018-02-01.通讯作者：陶凌，教授，主要从事心脏病基础与临床研究 Email：lingtao@fmmu.edu.cn 共同通讯作者：张富洋，讲师，博士，主要从事糖尿病心肌损伤基础研究 Email：plazhangfuyang@163.com 作者简介：姬宇飞，硕士生 Email：919276878@qq.com
更新日期/Last Update: 1900-01-01