Resveratrol inhibits high-glucose-induced inflammatory “metabolic memory” in human retinal vascular endothelial cells through SIRT1-dependent signaling

Oct 23, 2019Canadian journal of physiology and pharmacology

Resveratrol may reduce lasting inflammation caused by high sugar in human eye blood vessel cells through SIRT1-related signals

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Abstract

High glucose concentration significantly reduced human retinal vascular endothelial cell (HRVEC) viability.

High glucose exposure increased inflammation markers such as Acetylated nuclear factor κB (Ac-NF-κB) and NOD-like receptor family, pyrin domain containing 3 (NLRP3).
SIRT1 levels decreased in HRVECs exposed to high glucose, contributing to sustained inflammation.
Resveratrol enhanced HRVEC viability and decreased inflammatory cytokine levels in high glucose conditions.
The beneficial effects of resveratrol were inhibited by co-treatment with SIRT1 and AMPK inhibitors.
High glucose reduced AMP-activated protein kinase (AMPK) phosphorylation, which remained low during the reversal period.

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Diabetes induces vascular endothelial damage and this study investigated high-glucose-induced inflammation "metabolic memory" of human retinal vascular endothelial cells (HRVECs), the effects of resveratrol on HRVECs, and the underlying signaling. HRVECs were grown under various conditions and assayed for levels of sirtuin 1 (SIRT1); acetylated nuclear factor κB (Ac-NF-κB); NOD-like receptor family, pyrin domain containing 3 (NLRP3); and other inflammatory cytokines; and cell viability. A high glucose concentration induced HRVEC inflammation metabolic memory by decreasing SIRT1 and increasing Ac-NF-κB, NLRP3, caspase 1, interleukin-1β, inducible nitric oxide synthase, and tumor necrosis factor α, whereas exposure of HRVECs to a high glucose medium for 4 days, followed by a normal glucose concentration for an additional 4 days, failed to reverse these changes. A high glucose concentration also significantly reduced HRVEC viability. In contrast, resveratrol, a selective SIRT1 activator, markedly enhanced HRVEC viability and reduced the inflammatory cytokines expressions. In addition, high glucose reduced AMP-activated protein kinase (AMPK) phosphorylation and retained during the 4 days of the reversal period of culture. The effects of resveratrol were abrogated after co-treatment with the SIRT1 inhibitor nicotinamide and the AMPK inhibitor compound C. In conclusion, resveratrol was able to reverse high-glucose-induced inflammation "metabolic memory" of HRVECs by activation of the SIRT1/AMPK/NF-κB pathway.

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Resveratrol inhibits high-glucose-induced inflammatory “metabolic memory” in human retinal vascular endothelial cells through SIRT1-dependent signaling

Abstract

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