{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:00:16Z","timestamp":1791165616937,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Laboratory of Excellence LERMIT","award":["#ANR-10-LABX-33"],"award-info":[{"award-number":["#ANR-10-LABX-33"]}]},{"name":"Laboratory of Excellence LERMIT","award":["#DPM20121125546"],"award-info":[{"award-number":["#DPM20121125546"]}]},{"name":"Laboratory of Excellence LERMIT","award":["#FDT202001010787"],"award-info":[{"award-number":["#FDT202001010787"]}]},{"name":"FRM (Fondation pour la Recherche M\u00e9dicale)","award":["#ANR-10-LABX-33"],"award-info":[{"award-number":["#ANR-10-LABX-33"]}]},{"name":"FRM (Fondation pour la Recherche M\u00e9dicale)","award":["#DPM20121125546"],"award-info":[{"award-number":["#DPM20121125546"]}]},{"name":"FRM (Fondation pour la Recherche M\u00e9dicale)","award":["#FDT202001010787"],"award-info":[{"award-number":["#FDT202001010787"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Disturbances in Endoplasmic Reticulum (ER) homeostasis induce ER stress, which has been involved in the development and progression of various heart diseases, including arrhythmias, cardiac hypertrophy, ischemic heart diseases, dilated cardiomyopathy, and heart failure. A mild-to-moderate ER stress is considered beneficial and adaptative for heart functioning by engaging the pro-survival unfolded protein response (UPR) to restore normal ER function. By contrast, a severe or prolonged ER stress is detrimental by promoting cardiomyocyte apoptosis through hyperactivation of the UPR pathways. Previously, we have demonstrated that the NAD+-dependent deacetylase SIRT1 is cardioprotective in response to severe ER stress by regulating the PERK pathway of the UPR, suggesting that activation of SIRT1 could protect against ER-stress-induced cardiac damage. The purpose of this study was to identify natural molecules able to alleviate ER stress and inhibit cardiomyocyte cell death through SIRT1 activation. Several phenolic compounds, abundant in vegetables, fruits, cereals, wine, and tea, were reported to stimulate the deacetylase activity of SIRT1. Here, we evaluated the cardioprotective effect of ten of these phenolic compounds against severe ER stress using cardiomyoblast cells and mice. Among the molecules tested, we showed that ferulic acid, pterostilbene, and tyrosol significantly protect cardiomyocytes and mice heart from cardiac alterations induced by severe ER stress. By studying the mechanisms involved, we showed that the activation of the PERK\/eIF2\u03b1\/ATF4\/CHOP pathway of the UPR was reduced by ferulic acid, pterostilbene, and tyrosol under ER stress conditions, leading to a reduction in cardiomyocyte apoptosis. The protection afforded by these phenolic compounds was not directly related to their antioxidant activity but rather to their ability to increase SIRT1-mediated deacetylation of eIF2\u03b1. Taken together, our results suggest that ferulic acid, pterostilbene, and tyrosol are promising molecules to activate SIRT1 to protect the heart from the adverse effects of ER stress.<\/jats:p>","DOI":"10.3390\/ijms23126628","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T23:50:14Z","timestamp":1655250614000},"page":"6628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Ferulic Acid, Pterostilbene, and Tyrosol Protect the Heart from ER-Stress-Induced Injury by Activating SIRT1-Dependent Deacetylation of eIF2\u03b1"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8700-2986","authenticated-orcid":false,"given":"K\u00e9vin","family":"Monceaux","sequence":"first","affiliation":[{"name":"Facult\u00e9 de Pharmacie, UMR-S 1180, INSERM, Universit\u00e9 Paris-Saclay, 5 Rue J-B Cl\u00e9ment, 92296 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Gressette","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie, UMR-S 1180, INSERM, Universit\u00e9 Paris-Saclay, 5 Rue J-B Cl\u00e9ment, 92296 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Karoui","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie, UMR-S 1180, INSERM, Universit\u00e9 Paris-Saclay, 5 Rue J-B Cl\u00e9ment, 92296 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7718-7892","authenticated-orcid":false,"given":"Julie","family":"Pires Da Silva","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie, UMR-S 1180, INSERM, Universit\u00e9 Paris-Saclay, 5 Rue J-B Cl\u00e9ment, 92296 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6019-8683","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Piquereau","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie, UMR-S 1180, INSERM, Universit\u00e9 Paris-Saclay, 5 Rue J-B Cl\u00e9ment, 92296 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9e","family":"Ventura-Clapier","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie, UMR-S 1180, INSERM, Universit\u00e9 Paris-Saclay, 5 Rue J-B Cl\u00e9ment, 92296 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Garnier","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie, UMR-S 1180, INSERM, Universit\u00e9 Paris-Saclay, 5 Rue J-B Cl\u00e9ment, 92296 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6779-092X","authenticated-orcid":false,"given":"Mathias","family":"Mericskay","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie, UMR-S 1180, INSERM, Universit\u00e9 Paris-Saclay, 5 Rue J-B Cl\u00e9ment, 92296 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6316-8781","authenticated-orcid":false,"given":"Christophe","family":"Lemaire","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie, UMR-S 1180, INSERM, Universit\u00e9 Paris-Saclay, 5 Rue J-B Cl\u00e9ment, 92296 Ch\u00e2tenay-Malabry, France"},{"name":"Inserm, UMR-S 1180, Universit\u00e9 Versailles St-Quentin, Universit\u00e9 Paris-Saclay, 92296 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/febs.14608","article-title":"Endoplasmic reticulum stress signalling\u2014From basic mechanisms to clinical applications","volume":"286","author":"Almanza","year":"2019","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41580-020-0250-z","article-title":"Mechanisms, regulation and functions of the unfolded protein response","volume":"21","author":"Hetz","year":"2020","journal-title":"Nat. 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