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Article

SIRT1-Dependent Upregulation of Antiglycative Defense in HUVECs Is Essential for Resveratrol Protection against High Glucose Stress

1
Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
2
Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy
*
Authors to whom correspondence should be addressed.
Antioxidants 2019, 8(9), 346; https://doi.org/10.3390/antiox8090346
Received: 26 July 2019 / Revised: 9 August 2019 / Accepted: 26 August 2019 / Published: 1 September 2019
Uncontrolled accumulation of methylglyoxal (MG) and reactive oxygen species (ROS) occurs in hyperglycemia-induced endothelial dysfunction associated with diabetes. Resveratrol (RSV) protects the endothelium upon high glucose (HG); however, the mechanisms underlying such protective effects are still debated. Here we identified key molecular players involved in the glycative/oxidative perturbations occurring in endothelial cells exposed to HG. In addition, we determined whether RSV essentially required SIRT1 to trigger adaptive responses in HG-challenged endothelial cells. We used primary human umbilical vein endothelial cells (HUVECs) undergoing a 24-h treatment with HG, with or without RSV and EX527 (i.e., SIRT1 inhibitor). We found that HG-induced glycative stress (GS) and oxidative stress (OS), by reducing SIRT1 activity, as well as by diminishing the efficiency of MG- and ROS-targeting protection. RSV totally abolished the HG-dependent cytotoxicity, and this was associated with SIRT1 upregulation, together with increased expression of GLO1, improved ROS-scavenging efficiency, and total suppression of HG-related GS and OS. Interestingly, RSV failed to induce effective response to HG cytotoxicity when EX527 was present, thus suggesting that the upregulation of SIRT1 is essential for RSV to activate the major antiglycative and antioxidative defense and avoid MG- and ROS-dependent molecular damages in HG environment. View Full-Text
Keywords: oxidative stress; glycative stress; dicarbonyl stress; antioxidant defense; superoxide dismutase; catalase; glyoxalase; EX527; sirtuin 1 oxidative stress; glycative stress; dicarbonyl stress; antioxidant defense; superoxide dismutase; catalase; glyoxalase; EX527; sirtuin 1
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MDPI and ACS Style

Santini, S.J.; Cordone, V.; Mijit, M.; Bignotti, V.; Aimola, P.; Dolo, V.; Falone, S.; Amicarelli, F. SIRT1-Dependent Upregulation of Antiglycative Defense in HUVECs Is Essential for Resveratrol Protection against High Glucose Stress. Antioxidants 2019, 8, 346. https://doi.org/10.3390/antiox8090346

AMA Style

Santini SJ, Cordone V, Mijit M, Bignotti V, Aimola P, Dolo V, Falone S, Amicarelli F. SIRT1-Dependent Upregulation of Antiglycative Defense in HUVECs Is Essential for Resveratrol Protection against High Glucose Stress. Antioxidants. 2019; 8(9):346. https://doi.org/10.3390/antiox8090346

Chicago/Turabian Style

Santini, Silvano J., Valeria Cordone, Mahmut Mijit, Virginio Bignotti, Pierpaolo Aimola, Vincenza Dolo, Stefano Falone, and Fernanda Amicarelli. 2019. "SIRT1-Dependent Upregulation of Antiglycative Defense in HUVECs Is Essential for Resveratrol Protection against High Glucose Stress" Antioxidants 8, no. 9: 346. https://doi.org/10.3390/antiox8090346

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