Drug screening for autophagy inhibitors based on the dissociation of Beclin1-Bcl2 complex using BiFC technique and mechanism of eugenol on anti-influenza A virus activity.
Drug screening for autophagy inhibitors based on the dissociation of Beclin1-Bcl2 complex using BiFC technique and mechanism of eugenol on anti-influenza A virus activity.
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BiFC技术基于Beclin1-Bcl2复合物解离的自噬抑制剂药物筛选及丁子香酚抗甲型流感病毒活性机制
DOI：
10.1371/journal.pone.0061026
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li KS
中科院分区：
文献类型：
--
作者：
Dai JP;Zhao XF;Zeng J;Wan QY;Yang JC;Li WZ;Chen XX;Wang GF;Li KS
Autophagy is involved in many human diseases, such as cancer, cardiovascular disease and virus infection, including human immunodeficiency virus (HIV), hepatitis C virus (HCV), influenza A virus (IAV) and coxsackievirus B3/B4 (CVB3/B4), so a drug screening model targeting autophagy may be very useful for the therapy of these diseases. In our study, we established a drug screening model based on the inhibition of the dissociation of Beclin1-Bcl2 heterodimer, an important negative regulator of autophagy, using bimolecular fluorescence complementation (BiFC) technique for developing novel autophagy inhibitors and anti-IAV agents. From 86 examples of traditional Chinese medicines, we found Syzygium aromaticum L. had the best activity. We then determined the anti-autophagy and anti-IAV activity of eugenol, the major active compound of Syzygium aromaticum L., and explored its mechanism of action. Eugenol could inhibit autophagy and IAV replication, inhibited the activation of ERK, p38MAPK and IKK/NF-κB signal pathways and antagonized the effects of the activators of these pathways. Eugenol also ameliorated the oxidative stress and inhibited the expressions of autophagic genes. We speculated that the mechanism underlying might be that eugenol inhibited the oxidative stress and the activation of ERK1/2, p38MAPK and IKK/NF-κB pathways, subsequently inhibited the dissociation of Beclin1-Bcl2 heterodimer and autophagy, and finally impaired IAV replication. These results might conversely display the reasonableness of the design of our screening model. In conclusion, we have established a drug screening model for developing novel autophagy inhibitor, and find eugenol as a promising inhibitor for autophagy and IAV infection.
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影响因子：
--
作者：
Müller B;Kräusslich HG
通讯作者：
Kräusslich HG
影响因子：
6.7
作者：
Grégoire IP;Richetta C;Meyniel-Schicklin L;Borel S;Pradezynski F;Diaz O;Deloire A;Azocar O;Baguet J;Le Breton M;Mangeot PE;Navratil V;Joubert PE;Flacher M;Vidalain PO;André P;Lotteau V;Biard-Piechaczyk M;Rabourdin-Combe C;Faure M
通讯作者：
Faure M
影响因子：
6.6
作者：
Hariharan, Nirmala;Zhai, Peiyong;Sadoshima, Junichi
通讯作者：
Sadoshima, Junichi
DOI：
10.1360/062004-69
发表时间：
2005-02-01
期刊：
SCIENCE IN CHINA SERIES C-LIFE SCIENCES
影响因子：
--
作者：
Liu, AL;Cao, HP;Du, GH
通讯作者：
Du, GH
探索神经氨酸酶突变体中Zanamivir抗性的机制：一项分子动力学研究。
影响因子：
3.7
作者：
Han N;Liu X;Mu Y
通讯作者：
Mu Y