StressCovidV1, Main, Exploration, bibRecord, 001085

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.

Identifieur interne : 001085 ( Main/Exploration ); précédent : 001084; suivant : 001086

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.

Auteurs : Jian-Ping Dai [République populaire de Chine] ; Xiang-Feng Zhao ; Jun Zeng ; Qian-Ying Wan ; Jia-Cai Yang ; Wei-Zhong Li ; Xiao-Xuan Chen ; Ge-Fei Wang ; Kang-Sheng Li

Source :

PloS one [ 1932-6203 ] ; 2013.

RBID : pubmed:23613775

Descripteurs français

KwdFr :
- Antiviraux (pharmacologie), Autophagie (), Eugénol (pharmacologie), Humains, Lignée cellulaire, Médicaments issus de plantes chinoises (pharmacologie), Syzygium (), Virus de la grippe A (), Évaluation préclinique de médicament ().
MESH :
- pharmacologie : Antiviraux, Eugénol, Médicaments issus de plantes chinoises.
- Autophagie, Humains, Lignée cellulaire, Syzygium, Virus de la grippe A, Évaluation préclinique de médicament.

English descriptors

KwdEn :
- Antiviral Agents (pharmacology), Autophagy (drug effects), Cell Line, Drug Evaluation, Preclinical (methods), Drugs, Chinese Herbal (pharmacology), Eugenol (pharmacology), Humans, Influenza A virus (drug effects), Syzygium (chemistry).
MESH :
- chemical , pharmacology : Antiviral Agents, Drugs, Chinese Herbal, Eugenol.
- chemistry : Syzygium.
- drug effects : Autophagy, Influenza A virus.
- methods : Drug Evaluation, Preclinical.
- Cell Line, Humans.

Abstract

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.

DOI: 10.1371/journal.pone.0061026
PubMed: 23613775

Affiliations:

République populaire de Chine

Le document en format XML

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<front><div type="abstract" xml:lang="en">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.</div>
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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.

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

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