Regulation of SIRT1 and Its Roles in Inflammation

Yang, Yunshu; Liu, Yang; Wang, Yunwei; Chao, Yongyi; Zhang, Jinxin; Jia, Yong; Tie, Jun; Hu, Dahai

doi:10.3389/fimmu.2022.831168

Cited by 171 publications

(143 citation statements)

References 175 publications

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“…Sirt is an NAD + -dependent deacetylase and ADP-ribosyltransferase related to energy metabolism and senescence [ 56 , 57 ]. Sirt1 is the most extensively studied protein and is mainly located in the cytoplasm and nucleus [ 58 ]. Sirt1 regulates oxidative stress by deacetylating Pgc-1 α and contributing to Nrf2 transcription in chromium-induced lung injury [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Acetylation of Atp5f1c Mediates Cardiomyocyte Senescence via Metabolic Dysfunction in Radiation-Induced Heart Damage

Zeng

et al. 2022

Oxidative Medicine and Cellular Longevity

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Objective Ionizing radiation (IR) causes cardiac senescence, which eventually manifests as radiation-induced heart damage (RIHD). This study is aimed at exploring the mechanisms underlying IR-induced senescence using acetylation proteomics. Methods Irradiated mouse hearts and H9C2 cells were harvested for senescence detection. Acetylation proteomics was used to investigate alterations in lysine acetylation. Atp5f1c acetylation after IR was verified using coimmunoprecipitation (Co-IP). Atp5f1c lysine 55 site acetylation (Atp5f1c K55-Ac) point mutation plasmids were used to evaluate the influence of Atp5f1c K55-Ac on energy metabolism and cellular senescence. Deacetylation inhibitors, plasmids, and siRNA transfection were used to determine the mechanism of Atp5f1c K55-Ac regulation. Results The mice showed cardiomyocyte and cardiac aging phenotypes after IR. We identified 90 lysine acetylation sites from 70 protein alterations in the heart in response to IR. Hyperacetylated proteins are primarily involved in energy metabolism. Among them, Atp5f1c was hyperacetylated, as confirmed by Co-IP. Atp5f1c K55-Ac decreased ATP enzyme activity and synthesis. Atp5f1c K55 acetylation induced cardiomyocyte senescence, and Sirt4 and Sirt5 regulated Atp5f1c K55 deacetylation. Conclusion Our findings reveal a mechanism of RIHD through which Atp5f1c K55-Ac leads to cardiac aging and Sirt4 or Sirt5 modulates Atp5f1c acetylation. Therefore, the regulation of Atp5f1c K55-Ac might be a potential target for the treatment of RIHD.

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Section: Discussionmentioning

confidence: 99%

Acetylation of Atp5f1c Mediates Cardiomyocyte Senescence via Metabolic Dysfunction in Radiation-Induced Heart Damage

Zeng

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Sirtuins (SIRTs) are a family of nicotinamide adenine dinucleotide (NAD + )-dependent histone deacetylases composed of seven isoforms (SIRT1-SIRT7), which are involved in many pathophysiological processes including inflammation, fibrosis, atherosclerosis, energy metabolism, aging-related diseases and cancers ( Grootaert and Bennett, 2022 ; Huang et al, 2022 ; Yang et al, 2022 ). SIRT1 activity has been shown to be decreased in several septic animal models.…”

Section: Autophagy In Sepsis-induced Acute Kidney Injurymentioning

confidence: 99%

Sepsis-induced AKI: From pathogenesis to therapeutic approaches

Wang

Chen

et al. 2022

Front. Pharmacol.

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Sepsis is a heterogenous and highly complex clinical syndrome, which is caused by infectious or noninfectious factors. Acute kidney injury (AKI) is one of the most common and severe complication of sepsis, and it is associated with high mortality and poor outcomes. Recent evidence has identified that autophagy participates in the pathophysiology of sepsis-associated AKI. Despite the use of antibiotics, the mortality rate is still at an extremely high level in patients with sepsis. Besides traditional treatments, many natural products, including phytochemicals and their derivatives, are proved to exert protective effects through multiple mechanisms, such as regulation of autophagy, inhibition of inflammation, fibrosis, and apoptosis, etc. Accumulating evidence has also shown that many pharmacological inhibitors might have potential therapeutic effects in sepsis-induced AKI. Hence, understanding the pathophysiology of sepsis-induced AKI may help to develop novel therapeutics to attenuate the complications of sepsis and lower the mortality rate. This review updates the recent progress of underlying pathophysiological mechanisms of sepsis-associated AKI, focuses specifically on autophagy, and summarizes the potential therapeutic effects of phytochemicals and pharmacological inhibitors.

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“…24S-HC, an oxysterol highly detected in brain and microglia (a macrophage population in the central nervous system), is capable of activating silent information regulator-1 (SIRT1), a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase by inducing a cell redox imbalance [ 75 , 76 ]. SIRT1 can inhibit gene expression of pro-inflammatory molecules through histone deacetylation, suggesting that 24S-HC could have anti-inflammatory property [ 77 ]. Taken together, several oxysterols modulate inflammation by epigenetic and epigenomic modification.…”

Section: The Impact Of Cholesterol and Oxysterols On Immune Cellsmentioning

confidence: 99%

The Impacts of Cholesterol, Oxysterols, and Cholesterol Lowering Dietary Compounds on the Immune System

Yanagisawa

Asai

et al. 2022

IJMS

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Cholesterol and its oxidized forms, oxysterols, are ingested from foods and are synthesized de novo. Cholesterol and oxysterols influence molecular and cellular events and subsequent biological responses of immune cells. The amount of dietary cholesterol influence on the levels of LDL cholesterol and blood oxysterols plays a significant role in the induction of pro-inflammatory state in immune cells, leading to inflammatory disorders, including cardiovascular disease. Cholesterol and oxysterols synthesized de novo in immune cells and stroma cells are involved in immune homeostasis, which may also be influenced by an excess intake of dietary cholesterol. Dietary compounds such as β-glucan, plant sterols/stanols, omega-3 lipids, polyphenols, and soy proteins, could lower blood cholesterol levels by interfering with cholesterol absorption and metabolism. Such dietary compounds also have potential to exert immune modulation through diverse mechanisms. This review addresses current knowledge about the impact of dietary-derived and de novo synthesized cholesterol and oxysterols on the immune system. Possible immunomodulatory mechanisms elicited by cholesterol-lowering dietary compounds are also discussed.

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Regulation of SIRT1 and Its Roles in Inflammation

Cited by 171 publications

References 175 publications

Acetylation of Atp5f1c Mediates Cardiomyocyte Senescence via Metabolic Dysfunction in Radiation-Induced Heart Damage

Acetylation of Atp5f1c Mediates Cardiomyocyte Senescence via Metabolic Dysfunction in Radiation-Induced Heart Damage

Sepsis-induced AKI: From pathogenesis to therapeutic approaches

The Impacts of Cholesterol, Oxysterols, and Cholesterol Lowering Dietary Compounds on the Immune System

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