IR@PKUHSC  > 北京大学基础医学院  > 心血管所
学科主题基础医学
Cross Regulation Between cGMP-dependent Protein Kinase and Akt in Vasodilatation of Porcine Pulmonary Artery
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
2014-11-01
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
WOS记录号WOS:000345102200008
Citation statistics
Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64818
Collection北京大学基础医学院_心血管所
北京大学基础医学院
北京大学第一临床医学院_急诊科
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
GB/T 7714
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.
APA Liu, Juan.,Liu, Huixia.,Li, Yanjing.,Xu, Xiaojian.,Chen, Zhengju.,...&Dou, Dou.(2014).Cross Regulation Between cGMP-dependent Protein Kinase and Akt in Vasodilatation of Porcine Pulmonary Artery.JOURNAL OF CARDIOVASCULAR PHARMACOLOGY,64(5),452-459.
MLA Liu, Juan,et al."Cross Regulation Between cGMP-dependent Protein Kinase and Akt in Vasodilatation of Porcine Pulmonary Artery".JOURNAL OF CARDIOVASCULAR PHARMACOLOGY 64.5(2014):452-459.
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