Selective and sensitive fluorescence imaging reveals microenvironment-dependent behavior of NO modulators in the endothelial system
文献类型：期刊论文
| 作者 | Dong, Ying2,3; Li, Xiao-Rong1; Li, Jia2,3,4 ; Zang, Yi2,3; Li, Xin1
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| 刊名 | JOURNAL OF PHARMACEUTICAL ANALYSIS
 |
| 出版日期 | 2020-10-01 |
| 卷号 | 10期号:5页码:466-472 |
| 关键词 | Nitric oxide modulator Drug screen Fluorescence imaging Microenvironment Endothelial cell |
| ISSN号 | 2095-1779 |
| DOI | 10.1016/j.jpha.2020.05.010 |
| 通讯作者 | Zang, Yi(yzang@simm.ac.cn) ; Li, Xin(lixin81@zju.edu.cn) |
| 英文摘要 | Nitric oxide (NO) is a second messenger playing crucial roles in the signaling of a variety of cellular functions. Due to its pathophysiological significance, various NO modulators have been developed to explore NO pathways and some have been used as therapies. These modulators are often used directly to observe pharmacological effects in cell lines, but their actual effect on intracellular NO level is seldom analyzed. Herein, facilitated by a selective and sensitive fluorescence probe, we observed that some NO modulators displayed unexpected behaviors with both NO scavenger carboxy-PTIO and endothelial nitric oxide synthase (eNOS) inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) failing to decrease intracellular free NO level in EA. hy926 cells while NO donor diethylamine-NONOate (DEA.NONOate) and eNOS activator calcimycin (A23187) failing to increase free NO level in human umbilical vein endothelial cell line (HUV-EC-C), although the reagents were confirmed to work normally in the primary human umbilical vein endothelial cells (primary HUVECs) and RAW 264.7 macrophage cells. Further research suggested that these unusual behaviors might be attributed to the cellular microenvironments including both the NO synthase (NOS) level and the endogenous glutathione (GSH) level. Genetically manipulating eNOS level in both cells restores the expected response, while decreasing GSH level restores the ability of DEA.NONOate to increase NO level in HUV-EC-C. These results reveal that the cellular microenvironment has a profound impact on pharmacological effect. Our study suggests GSH as a reservoir for NO in live cells and highlights the value of chemical probes as valuable tools to reveal microenvironment-dependent pharmacological effects. (C) 2020 Xi'an Jiaotong University. Production and hosting by Elsevier B.V. |
| WOS关键词 | NITRIC-OXIDE SYNTHASE ; MOLECULAR-CLONING ; EXPRESSION ; PATHWAY ; PROBE |
| 资助项目 | National Natural Science Foundations of China[21778048] ; National Natural Science Foundations of China[81673489] ; National Natural Science Foundations of China[31871414] ; National Natural Science Foundations of China[U1703235] ; National Key R&D Program of China[2019ZX09201001-003-010] ; Natural Science Foundation of Zhejiang Province, China[LR18H300001] ; Shanghai Science and Technology Development Funds[19YF1457500] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000582978400008 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/291035]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zang, Yi; Li, Xin |
| 作者单位 | 1.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Pilot Natl Lab Marine Sci & Technol Qingdao, Open Studio Draggabil Res Marine Nat Prod, 1 Wenhai Rd, Qingdao 266237, Peoples R China |
| 推荐引用方式 GB/T 7714 | Dong, Ying,Li, Xiao-Rong,Li, Jia,et al. Selective and sensitive fluorescence imaging reveals microenvironment-dependent behavior of NO modulators in the endothelial system[J]. JOURNAL OF PHARMACEUTICAL ANALYSIS,2020,10(5):466-472. |
| APA | Dong, Ying,Li, Xiao-Rong,Li, Jia,Zang, Yi,&Li, Xin.(2020).Selective and sensitive fluorescence imaging reveals microenvironment-dependent behavior of NO modulators in the endothelial system.JOURNAL OF PHARMACEUTICAL ANALYSIS,10(5),466-472. |
| MLA | Dong, Ying,et al."Selective and sensitive fluorescence imaging reveals microenvironment-dependent behavior of NO modulators in the endothelial system".JOURNAL OF PHARMACEUTICAL ANALYSIS 10.5(2020):466-472. |
入库方式： OAI收割
来源：上海药物研究所
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