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Назив: 3,4-Dimethoxychalcone induces autophagy through activation of the transcription factors TFE3 and TFEB
Аутори: Chen G.
Xie W.
Nah J.
Sauvat A.
Liu P.
Pietrocola F.
Sica V.
Carmona-Gutierrez D.
Zimmermann A.
Pendl T.
Tadic J.
Bergmann M.
Hofer S.
Domuz, Lana
Lachkar S.
Markaki M.
Tavernarakis N.
Sadoshima J.
Madeo F.
Kepp O.
Kroemer G.
Датум издавања: 7-нов-2019
Часопис: EMBO Molecular Medicine
Сажетак: © 2019 The Authors. Published under the terms of the CC BY 4.0 license Caloric restriction mimetics (CRMs) are natural or synthetic compounds that mimic the health-promoting and longevity-extending effects of caloric restriction. CRMs provoke the deacetylation of cellular proteins coupled to an increase in autophagic flux in the absence of toxicity. Here, we report the identification of a novel candidate CRM, namely 3,4-dimethoxychalcone (3,4-DC), among a library of polyphenols. When added to several different human cell lines, 3,4-DC induced the deacetylation of cytoplasmic proteins and stimulated autophagic flux. At difference with other well-characterized CRMs, 3,4-DC, however, required transcription factor EB (TFEB)- and E3 (TFE3)-dependent gene transcription and mRNA translation to trigger autophagy. 3,4-DC stimulated the translocation of TFEB and TFE3 into nuclei both in vitro and in vivo, in hepatocytes and cardiomyocytes. 3,4-DC induced autophagy in vitro and in mouse organs, mediated autophagy-dependent cardioprotective effects, and improved the efficacy of anticancer chemotherapy in vivo. Altogether, our results suggest that 3,4-DC is a novel CRM with a previously unrecognized mode of action.
URI: https://open.uns.ac.rs/handle/123456789/14149
ISSN: 17574676
DOI: 10.15252/emmm.201910469
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