Ferulic Acid, Pterostilbene, and Tyrosol Protect the Heart from ER-Stress-Induced Injury by Activating SIRT1-Dependent Deacetylation of eIF2α
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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/12/6628 |
| _version_ | 1797486485449998336 |
|---|---|
| author | Kévin Monceaux Mélanie Gressette Ahmed Karoui Julie Pires Da Silva Jérôme Piquereau Renée Ventura-Clapier Anne Garnier Mathias Mericskay Christophe Lemaire |
| author_facet | Kévin Monceaux Mélanie Gressette Ahmed Karoui Julie Pires Da Silva Jérôme Piquereau Renée Ventura-Clapier Anne Garnier Mathias Mericskay Christophe Lemaire |
| author_sort | Kévin Monceaux |
| collection | DOAJ |
| description | 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<sup>+</sup>-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/eIF2α/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 eIF2α. 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. |
| first_indexed | 2024-03-09T23:33:50Z |
| format | Article |
| id | doaj.art-200a60355617416fb55f3cf330a6bf92 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:33:50Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-200a60355617416fb55f3cf330a6bf922023-11-23T17:04:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012312662810.3390/ijms23126628Ferulic Acid, Pterostilbene, and Tyrosol Protect the Heart from ER-Stress-Induced Injury by Activating SIRT1-Dependent Deacetylation of eIF2αKévin Monceaux0Mélanie Gressette1Ahmed Karoui2Julie Pires Da Silva3Jérôme Piquereau4Renée Ventura-Clapier5Anne Garnier6Mathias Mericskay7Christophe Lemaire8Faculté de Pharmacie, UMR-S 1180, INSERM, Université Paris-Saclay, 5 Rue J-B Clément, 92296 Châtenay-Malabry, FranceFaculté de Pharmacie, UMR-S 1180, INSERM, Université Paris-Saclay, 5 Rue J-B Clément, 92296 Châtenay-Malabry, FranceFaculté de Pharmacie, UMR-S 1180, INSERM, Université Paris-Saclay, 5 Rue J-B Clément, 92296 Châtenay-Malabry, FranceFaculté de Pharmacie, UMR-S 1180, INSERM, Université Paris-Saclay, 5 Rue J-B Clément, 92296 Châtenay-Malabry, FranceFaculté de Pharmacie, UMR-S 1180, INSERM, Université Paris-Saclay, 5 Rue J-B Clément, 92296 Châtenay-Malabry, FranceFaculté de Pharmacie, UMR-S 1180, INSERM, Université Paris-Saclay, 5 Rue J-B Clément, 92296 Châtenay-Malabry, FranceFaculté de Pharmacie, UMR-S 1180, INSERM, Université Paris-Saclay, 5 Rue J-B Clément, 92296 Châtenay-Malabry, FranceFaculté de Pharmacie, UMR-S 1180, INSERM, Université Paris-Saclay, 5 Rue J-B Clément, 92296 Châtenay-Malabry, FranceFaculté de Pharmacie, UMR-S 1180, INSERM, Université Paris-Saclay, 5 Rue J-B Clément, 92296 Châtenay-Malabry, FranceDisturbances 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<sup>+</sup>-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/eIF2α/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 eIF2α. 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.https://www.mdpi.com/1422-0067/23/12/6628UPRsirtuin 1phenolic compoundscardioprotectionapoptosis |
| spellingShingle | Kévin Monceaux Mélanie Gressette Ahmed Karoui Julie Pires Da Silva Jérôme Piquereau Renée Ventura-Clapier Anne Garnier Mathias Mericskay Christophe Lemaire Ferulic Acid, Pterostilbene, and Tyrosol Protect the Heart from ER-Stress-Induced Injury by Activating SIRT1-Dependent Deacetylation of eIF2α International Journal of Molecular Sciences UPR sirtuin 1 phenolic compounds cardioprotection apoptosis |
| title | Ferulic Acid, Pterostilbene, and Tyrosol Protect the Heart from ER-Stress-Induced Injury by Activating SIRT1-Dependent Deacetylation of eIF2α |
| title_full | Ferulic Acid, Pterostilbene, and Tyrosol Protect the Heart from ER-Stress-Induced Injury by Activating SIRT1-Dependent Deacetylation of eIF2α |
| title_fullStr | Ferulic Acid, Pterostilbene, and Tyrosol Protect the Heart from ER-Stress-Induced Injury by Activating SIRT1-Dependent Deacetylation of eIF2α |
| title_full_unstemmed | Ferulic Acid, Pterostilbene, and Tyrosol Protect the Heart from ER-Stress-Induced Injury by Activating SIRT1-Dependent Deacetylation of eIF2α |
| title_short | Ferulic Acid, Pterostilbene, and Tyrosol Protect the Heart from ER-Stress-Induced Injury by Activating SIRT1-Dependent Deacetylation of eIF2α |
| title_sort | ferulic acid pterostilbene and tyrosol protect the heart from er stress induced injury by activating sirt1 dependent deacetylation of eif2α |
| topic | UPR sirtuin 1 phenolic compounds cardioprotection apoptosis |
| url | https://www.mdpi.com/1422-0067/23/12/6628 |
| work_keys_str_mv | AT kevinmonceaux ferulicacidpterostilbeneandtyrosolprotecttheheartfromerstressinducedinjurybyactivatingsirt1dependentdeacetylationofeif2a AT melaniegressette ferulicacidpterostilbeneandtyrosolprotecttheheartfromerstressinducedinjurybyactivatingsirt1dependentdeacetylationofeif2a AT ahmedkaroui ferulicacidpterostilbeneandtyrosolprotecttheheartfromerstressinducedinjurybyactivatingsirt1dependentdeacetylationofeif2a AT juliepiresdasilva ferulicacidpterostilbeneandtyrosolprotecttheheartfromerstressinducedinjurybyactivatingsirt1dependentdeacetylationofeif2a AT jeromepiquereau ferulicacidpterostilbeneandtyrosolprotecttheheartfromerstressinducedinjurybyactivatingsirt1dependentdeacetylationofeif2a AT reneeventuraclapier ferulicacidpterostilbeneandtyrosolprotecttheheartfromerstressinducedinjurybyactivatingsirt1dependentdeacetylationofeif2a AT annegarnier ferulicacidpterostilbeneandtyrosolprotecttheheartfromerstressinducedinjurybyactivatingsirt1dependentdeacetylationofeif2a AT mathiasmericskay ferulicacidpterostilbeneandtyrosolprotecttheheartfromerstressinducedinjurybyactivatingsirt1dependentdeacetylationofeif2a AT christophelemaire ferulicacidpterostilbeneandtyrosolprotecttheheartfromerstressinducedinjurybyactivatingsirt1dependentdeacetylationofeif2a |