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Hydrogen sulfide upregulates K-ATP channel expression in vascular smooth muscle cells of spontaneously hypertensive rats
Sun, Yan1; Huang, Yaqian1; Zhang, Rongyuan1; Chen, Qinghua1; Chen, Jie2; Zong, Yanfang1; Liu, Jia1; Feng, Shasha1; Liu, Angie Dong3; Holmberg, Lukas3; Liu, Die1; Tang, Chaoshu4,5; Du, Junbao1,5; Jin, Hongfang1
关键词Hydrogen Sulfide Vasorelaxation Atp-sensitive Potassium Channels Smooth Muscle Cell Hypertension
刊名JOURNAL OF MOLECULAR MEDICINE-JMM
2015-04-01
DOI10.1007/s00109-014-1227-1
93期:4页:439-455
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Genetics & Heredity ; Medicine, Research & Experimental
研究领域[WOS]Genetics & Heredity ; Research & Experimental Medicine
关键词[WOS]NITRIC-OXIDE ; POTASSIUM CHANNELS ; H2S ; KIR6.1 ; MICE ; GAS ; CARDIOMYOCYTES ; VASORELAXANT ; PATHOGENESIS ; REAPPRAISAL
英文摘要

The study was designed to investigate whether H2S could upregulate expression of K-ATP channels in vascular smooth muscle cells (VSMCs), and by this mechanism enhances vasorelaxation in spontaneously hypertensive rats (SHR). Blood pressure, vascular structure, and vasorelaxation were analyzed. Plasma H2S was detected using polarographic sensor. SUR2B and Kir6.1 expressions were detected in VSMCs of SHR and in A7r5 cells as well as primarily cultured ASMCs using real-time PCR, western blot, immunofluorescence, and confocal imaging. Nuclear translocation of forkhead transcription factors FOXO1 and FOXO3a in ASMCs was detected using laser confocal microscopy, and their binding activity with SUR2B and Kir6.1 promoters was examined by chromatin immunoprecipitation. SHR developed hypertension at 18 weeks. They showed downregulated vascular SUR2B and Kir6.1 expressions in association with a decreased plasma H2S level. H2S donor, however, could upregulate vascular SUR2B and Kir6.1 expressions, causing a left shift of the vasorelaxation curve to pinacidil and lowered tail artery pressure in the SHR. Also, H2S antagonized endothelin-1 (ET-1)-inhibited K-ATP expression in A7r5 cells and cultured ASMCs. Mechanistically, H2S inhibited ET-1-stimulated p-FOXO1 and p-FOXO3a expressions (inactivated forms), but increased their nuclear translocation and the ET-1-inhibited binding of FOXO1 and FOXO3a with Kir6.1 and SUR2B promoters in ASMCs. Hence, H2S promotes vasorelaxation of SHR, at least in part, through upregulating the expression of K-ATP subunits by inhibiting phosphorylation of FOXO1 and FOXO3a, and stimulating FOXO1 and FOXO3a nuclear translocation and their binding activity with SUR2B and Kir6.1 promoters.

H2S increased vascular SUR2B and Kir6.1 expression of SHR, promoting vasorelaxation.

H2S antagonized ET-1-inhibited K-ATP expression in A7r5 cells and cultured ASMCs.

H2S inhibited ET-1-induced FOXO1 and FOXO3a phosphorylation in ASMCs.

H2S promoted FOXO1 and FOXO3a nuclear translocation and binding with target gene promoters.

语种英语
WOS记录号WOS:000351518100009
项目编号2012CB517806 ; 2013CB933801 ; 81100181 ; 81121061 ; 7121014 ; 7122184 ; 20130001120047 ; NCET-11-0005
资助机构Major Basic Research Development Program of People&prime ; s Republic of China ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Ministry of Education, China ; Program for New Century Excellent Talents of Ministry of Education, China
引用统计
被引频次:18[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55304
专题北京大学第一临床医学院_儿科
作者单位1.Peking Univ First Hosp, Dept Pediat, Beijing 100034, Peoples R China
2.Fujian Med Univ, Prov Sch Clin Med, Dept Pediat, Fuzhou, Peoples R China
3.Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden
4.Peking Univ First Hosp, Inst Cardiovasc Dis, Beijing, Peoples R China
5.Minist Educ, Key Lab Mol Cardiol, Beijing, Peoples R China
推荐引用方式
GB/T 7714
Sun, Yan,Huang, Yaqian,Zhang, Rongyuan,et al. Hydrogen sulfide upregulates K-ATP channel expression in vascular smooth muscle cells of spontaneously hypertensive rats[J]. JOURNAL OF MOLECULAR MEDICINE-JMM,2015,93(4):439-455.
APA Sun, Yan.,Huang, Yaqian.,Zhang, Rongyuan.,Chen, Qinghua.,Chen, Jie.,...&Jin, Hongfang.(2015).Hydrogen sulfide upregulates K-ATP channel expression in vascular smooth muscle cells of spontaneously hypertensive rats.JOURNAL OF MOLECULAR MEDICINE-JMM,93(4),439-455.
MLA Sun, Yan,et al."Hydrogen sulfide upregulates K-ATP channel expression in vascular smooth muscle cells of spontaneously hypertensive rats".JOURNAL OF MOLECULAR MEDICINE-JMM 93.4(2015):439-455.
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