Scutellarin's Cardiovascular Endothelium Protective Mechanism: Important Role of PKG-I alpha

doi:10.1371/journal.pone.0139570

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	Scutellarin's Cardiovascular Endothelium Protective Mechanism: Important Role of PKG-I alpha
	Li, Lin 1,2,4; Li, Lu 2,3,4; Chen, Chen 2,4; Yang, Jian 2,4; Li, Jiaxun 2,4; Hu, Na 2,4; Li, Yang2,4 ; Zhang, Dongmei 3; Guo, Tao 1; Liu, Xuan 3
刊名	PLOS ONE
	2015-10-06
卷号	10 期号:10
ISSN号	1932-6203
DOI	10.1371/journal.pone.0139570
文献子类	Article
英文摘要	Scutellarin (SCU), a flavonoid glycoside compound, has been successfully used in clinic for treatment of ischemic diseases in China. In this report, we checked the effects of SCU on endothelium dysfunction (ED) of coronary artery (CA) against myocardial ischemia reperfusion (MIR) injury in vivo. The involvement of PKG-I alpha was further studied using cultured endothelial cells subjected to hypoxia reoxygenation (HR) injury in vitro. In rat MIR model, SCU (45 and 90 mg/kg, iv) significantly reduced ischemic size and restored the endothelium-dependent vasodilation of isolated CA rings. PKG inhibitor Rp-8-Br-cGMP (50 mu g/kg, iv) could ameliorate the protective effects of SCU. Increase in phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a main substrate of PKG, at Ser 239 was observed in both heart tissue and serum of SCU-treated animals. In cultured human cardiac microvascular endothelial cells (HCMECs), SCU (1 and 10 mu M) dose-dependently protected cell viability and increased the mRNA and protein level of PKG-I alpha against HR injury. The activity of PKG was also increased by SCU treatment. The activation of PKG-1 alpha was then studied using targeted proteomic analysis (MRM-MS) checking the phosphorylation state of the autophosphorylation domain (aa42-94). Significant decrease in phosphorylation of PKG-I alpha at Ser50, Ser72, Ser89 was induced by HR injury while SCU treatment significantly increased the phosphorylation of PKG-I alpha, not only at Ser50, Ser72 and Ser89, but also at Ser44 and Thr58 (two novel phosphorylation domains). Our results demonstrate PKG-I alpha might play an important role in the protective effects of SCU on ED against MIR injury.
资助项目	National Natural Science Foundation of China[30960450] ; National Natural Science Foundation of China[81173110] ; National Natural Science Foundation of China[81260027] ; National Natural Science Foundation of China[81560589] ; National Natural Science Foundation of China[81560072] ; Yunnan Provincial Science and Technology Department[2011FA022] ; Yunnan Provincial Science and Technology Department[2014FA010] ; Yunnan Provincial Science and Technology Department[2014BC012] ; Yunnan Provincial Science and Technology Department[2014FB037] ; Yunnan Provincial Science and Technology Department[2008CD054] ; Yunnan Provincial Science and Technology Department[2008ZC111M]
WOS关键词	DEPENDENT PROTEIN-KINASE ; MYOCARDIAL ISCHEMIA-REPERFUSION ; OVARIAN-CANCER CELLS ; NITRIC-OXIDE ; CYCLIC-GMP ; INDEPENDENT RELAXATION ; VASCULAR ENDOTHELIUM ; BAICALENSIS GEORGI ; CEREBRAL-ISCHEMIA ; OXIDATIVE STRESS
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000362510300032
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276368]
专题	上海中药现代化研究中心
通讯作者	Liu, Xuan
作者单位	1.Kunming Med Univ, Dept Cardiol, Affiliated Hosp 1, Kunming, Peoples R China; 2.Kunming Med Univ, Yunnan Key Lab Pharmacol Nat Prod, Kunming, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China 4.Kunming Med Univ, Sch Pharmaceut Sci, Kunming, Peoples R China;
推荐引用方式 GB/T 7714	Li, Lin,Li, Lu,Chen, Chen,et al. Scutellarin's Cardiovascular Endothelium Protective Mechanism: Important Role of PKG-I alpha[J]. PLOS ONE,2015,10(10).
APA	Li, Lin.,Li, Lu.,Chen, Chen.,Yang, Jian.,Li, Jiaxun.,...&Yang, Weimin.(2015).Scutellarin's Cardiovascular Endothelium Protective Mechanism: Important Role of PKG-I alpha.PLOS ONE,10(10).
MLA	Li, Lin,et al."Scutellarin's Cardiovascular Endothelium Protective Mechanism: Important Role of PKG-I alpha".PLOS ONE 10.10(2015).