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学科主题: 基础医学
题名:
Cross Regulation Between cGMP-dependent Protein Kinase and Akt in Vasodilatation of Porcine Pulmonary Artery
作者: Liu, Juan1; Liu, Huixia1,2; Li, Yanjing1; Xu, Xiaojian1; Chen, Zhengju1; Liu, Limei1,3; Yu, Xiaoxing1; Gao, Yuansheng1,3; Dou, Dou1,3
关键词: nitric oxide ; cGMP-dependent protein kinase ; Akt ; vasodilatation
刊名: JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
发表日期: 2014-11-01
卷: 64, 期:5, 页:452-459
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cardiac & Cardiovascular Systems ; Pharmacology & Pharmacy
研究领域[WOS]: Cardiovascular System & Cardiology ; Pharmacology & Pharmacy
关键词[WOS]: HIGH-ALTITUDE HYPOXIA ; NITRIC-OXIDE ; PHOSPHOINOSITIDE 3-KINASE ; INDUCED RELAXATION ; SMOOTH-MUSCLE ; CA2+ CHANNELS ; PHOSPHODIESTERASE PDE5 ; CELL-PROLIFERATION ; CORONARY-ARTERIES ; OKADAIC ACID
英文摘要:

cGMP-dependent protein kinase (PKG) plays a crucial role in vasodilatation induced by cGMP-elevating agents. Akt has been demonstrated to be involved in modulating vasoreactivity. The present study was to determine the interaction between PKG and Akt and their influences on nitric oxide (NO)-induced vasodilatation. Isolated fourth-generation porcine pulmonary arteries were dissected from the lung and cut into rings in ice-cold modified Krebs-Ringer bicarbonate buffer. The relaxant responses of vessels were determined by organ chamber technique, cGMP was assayed by using enzyme-linked immunosorbent assay kit, the protein levels of phosphorylated Akt were examined by Western blotting, and the activity of phosphodiesterase type 5 (PDE5) was assayed by measuring the rate of cGMP degradation. Incubation with DETA NONOate (a stable NO donor) and 8-Br-cGMP (a cell membrane permeable analog of cGMP) attenuated Akt phosphorylation at Ser-473, which was prevented by Rp-8-Br-PET-cGMPS (a specific inhibitor of PKG) and calyculin A (an inhibitor of protein phosphatase 1 and 2A) but not by okadaic acid (a selective inhibitor of protein phosphatase 2A). Inhibition of Akt enhanced the relaxation and cGMP elevation of porcine pulmonary arteries induced by DETA NONOate or sodium nitroprusside, which was prevented by zaprinast, a specific inhibitor of PDE5. Incubation with LY294002 or Akt inhibitor reduced PDE5 activity in porcine pulmonary arteries. The present study indicates that PKG may attenuate Akt phosphorylation through protein phosphatase 1, which leads to an augmented cGMP elevation by inhibition of PDE5. The increased cGMP in turn activates PKG. Such a positive feedback may play an important role in NO-induced pulmonary vasodilatation.

语种: 英语
所属项目编号: 81001433 ; 81270341 ; 81373404 ; 20100001120037 ; YETP0054
项目资助者: National Natural Science Foundation of China ; Ministry of Education for New Teachers ; Beijing Higher Education Young Elite Teacher Project
WOS记录号: WOS:000345102200008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64818
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China
2.Heze Med Coll, Dept Physiol, Heze, Peoples R China
3.Peking Univ, Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China

Recommended Citation:
Liu, Juan,Liu, Huixia,Li, Yanjing,et al. Cross Regulation Between cGMP-dependent Protein Kinase and Akt in Vasodilatation of Porcine Pulmonary Artery[J]. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY,2014,64(5):452-459.
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