Autophagy-mediated metabolic effects of aspirin.

Autor: Castoldi F; Centre de Recherche des Cordeliers, INSERM U1138, Team 'Meta7bolism, Cancer & Immunity', Sorbonne Université, Université de Paris, Institut Universitaire de France, Paris, France.; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Humeau J; Centre de Recherche des Cordeliers, INSERM U1138, Team 'Meta7bolism, Cancer & Immunity', Sorbonne Université, Université de Paris, Institut Universitaire de France, Paris, France.; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Martins I; Centre de Recherche des Cordeliers, INSERM U1138, Team 'Meta7bolism, Cancer & Immunity', Sorbonne Université, Université de Paris, Institut Universitaire de France, Paris, France.; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Lachkar S; Centre de Recherche des Cordeliers, INSERM U1138, Team 'Meta7bolism, Cancer & Immunity', Sorbonne Université, Université de Paris, Institut Universitaire de France, Paris, France.; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Loew D; Institut Curie, PSL Research University, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique, 26 rue d'Ulm, Paris, 75248, Cedex 05, France., Dingli F; Institut Curie, PSL Research University, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique, 26 rue d'Ulm, Paris, 75248, Cedex 05, France., Durand S; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Enot D; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Bossut N; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Chery A; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Aprahamian F; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Demont Y; Centre de Recherche des Cordeliers, INSERM U1138, Team 'Meta7bolism, Cancer & Immunity', Sorbonne Université, Université de Paris, Institut Universitaire de France, Paris, France.; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Opolon P; Department of Experimental Pathology, INSERM Unit U981, Gustave Roussy, Université Paris-Sud Saclay, Villejuif, France., Signolle N; Department of Experimental Pathology, INSERM Unit U981, Gustave Roussy, Université Paris-Sud Saclay, Villejuif, France., Sauvat A; Centre de Recherche des Cordeliers, INSERM U1138, Team 'Meta7bolism, Cancer & Immunity', Sorbonne Université, Université de Paris, Institut Universitaire de France, Paris, France.; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Semeraro M; Centre d'Investigation Clinique-Unite de Recherche Clinique Paris Centre Necker-Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France., Bezu L; Centre de Recherche des Cordeliers, INSERM U1138, Team 'Meta7bolism, Cancer & Immunity', Sorbonne Université, Université de Paris, Institut Universitaire de France, Paris, France.; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Baracco EE; Centre de Recherche des Cordeliers, INSERM U1138, Team 'Meta7bolism, Cancer & Immunity', Sorbonne Université, Université de Paris, Institut Universitaire de France, Paris, France.; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Vacchelli E; Centre de Recherche des Cordeliers, INSERM U1138, Team 'Meta7bolism, Cancer & Immunity', Sorbonne Université, Université de Paris, Institut Universitaire de France, Paris, France.; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Pol JG; Centre de Recherche des Cordeliers, INSERM U1138, Team 'Meta7bolism, Cancer & Immunity', Sorbonne Université, Université de Paris, Institut Universitaire de France, Paris, France.; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Lévesque S; Centre de Recherche des Cordeliers, INSERM U1138, Team 'Meta7bolism, Cancer & Immunity', Sorbonne Université, Université de Paris, Institut Universitaire de France, Paris, France.; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Bloy N; Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA., Sica V; Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), Barcelona, Spain., Maiuri MC; Centre de Recherche des Cordeliers, INSERM U1138, Team 'Meta7bolism, Cancer & Immunity', Sorbonne Université, Université de Paris, Institut Universitaire de France, Paris, France.; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Kroemer G; Centre de Recherche des Cordeliers, INSERM U1138, Team 'Meta7bolism, Cancer & Immunity', Sorbonne Université, Université de Paris, Institut Universitaire de France, Paris, France. kroemer@orange.fr.; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. kroemer@orange.fr.; Pôle de Biologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France. kroemer@orange.fr.; Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China. kroemer@orange.fr.; Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden. kroemer@orange.fr., Pietrocola F; Karolinska Institute, Department of Bioscience and Nutrition, Huddinge, Sweden. federico.pietrocola@ki.se.
Jazyk: angličtina
Zdroj: Cell death discovery [Cell Death Discov] 2020 Nov 24; Vol. 6 (1), pp. 129. Date of Electronic Publication: 2020 Nov 24.
DOI: 10.1038/s41420-020-00365-0
Abstrakt: Salicylate, the active derivative of aspirin (acetylsalicylate), recapitulates the mode of action of caloric restriction inasmuch as it stimulates autophagy through the inhibition of the acetyltransferase activity of EP300. Here, we directly compared the metabolic effects of aspirin medication with those elicited by 48 h fasting in mice, revealing convergent alterations in the plasma and the heart metabolome. Aspirin caused a transient reduction of general protein acetylation in blood leukocytes, accompanied by the induction of autophagy. However, these effects on global protein acetylation could not be attributed to the mere inhibition of EP300, as determined by epistatic experiments and exploration of the acetyl-proteome from salicylate-treated EP300-deficient cells. Aspirin reduced high-fat diet-induced obesity, diabetes, and hepatosteatosis. These aspirin effects were observed in autophagy-competent mice but not in two different models of genetic (Atg4b -/- or Bcln1 +/- ) autophagy-deficiency. Aspirin also improved tumor control by immunogenic chemotherapeutics, and this effect was lost in T cell-deficient mice, as well as upon knockdown of an essential autophagy gene (Atg5) in cancer cells. Hence, the health-improving effects of aspirin depend on autophagy.
Databáze: MEDLINE
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