Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6

D’Onofrio, Nunzia; Servillo, Luigi; Giovane, Alfonso; Casale, Rosario; Vitiello, Mariateresa; Marfella, Raffaele; Paolisso, Giuseppe; Balestrieri, Maria Luisa

doi:10.1016/j.freeradbiomed.2016.04.013

Cited by 99 publications

(79 citation statements)

References 46 publications

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“…During I/R liver injury and high-glucose-induced oxidative stress, the expression of p66 Shc varies inversely with that of SIRT1 (41,203). SIRT1 overexpression increased mitochondria biogenesis and expression of CAT and GPx by peroxisome proliferator-activated receptor coactivator (PPAR) 1-a activation ( Fig.…”

Section: Oxidative Stress and Vascular Dysfunctionmentioning

confidence: 98%

“…2). Evidence of SIRT6 involvement in vascular protection comes from several studies showing that SIRT6 deficiency raises the expression of endothelial proinflammatory cytokines and increases NF-jB transcriptional activity (16,41,97,109). The protective effect of SIRT6 against premature endothelial senescence is exerted through a fine control of the expression of intercellular adhesion molecule-1 (ICAM-1), PAI-1, p21…”

Section: Redox Regulation Of Sirt6 In Vascular Protectionmentioning

confidence: 99%

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SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection

D’Onofrio¹,

Servillo²,

Balestrieri³

2018

Antioxidants & Redox Signaling

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274

238

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Significance: Oxidative stress represents the common hallmark of pathological conditions associated with cardiovascular disease (CVD), including atherosclerosis, heart failure, hypertension, aging, diabetes, and other vascular system-related diseases. The sirtuin (SIRT) family, comprising seven proteins (SIRT1-SIRT7) sharing a highly conserved nicotinamide adenine dinucleotide (NAD + )-binding catalytic domain, attracted a great attention for the past few years as stress adaptor and epigenetic enzymes involved in the cellular events controlling aging-related disorder, cancer, and CVD. Recent Advances: Among sirtuins, SIRT1 and SIRT6 are the best characterized for their protective roles against inflammation, vascular aging, heart disease, and atherosclerotic plaque development. This latest role has been only recently unveiled for SIRT6. Of interest, in recent years, complex signaling networks controlled by SIRT1 and SIRT6 common to stress resistance, vascular aging, and CVD have emerged. Critical Issues: We provide a comprehensive overview of recent developments on the molecular signaling pathways controlled by SIRT1 and SIRT6, two post-translational modifiers proven to be valuable tools to dampen inflammation and oxidative stress at the cardiovascular level. Future Directions: A deeper understanding of the epigenetic mechanisms through which SIRT1 and SIRT6 act in the signalings responsible for onset and development CVD is a prime scientific endeavor of the upcoming years. Multiple ''omic'' technologies will have widespread implications in understanding such mechanisms, speeding up the achievement of selective and efficient pharmacological modulation of sirtuins for future applications in the prevention and treatment of CVD. Antioxid. Redox Signal. 28, 711-732.

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Section: Oxidative Stress and Vascular Dysfunctionmentioning

confidence: 98%

Section: Redox Regulation Of Sirt6 In Vascular Protectionmentioning

confidence: 99%

SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection

D’Onofrio¹,

Servillo²,

Balestrieri³

2018

Antioxidants & Redox Signaling

Self Cite

274

238

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“…3 Furthermore, future investigations might be helpful in the elucidation of the possible effect of GabaBet on SIRT6 modulation. 10 Indeed, both SIRT1 and SIRT6, showing an established role in the protection against CVD and hGluc-induced endothelial senescence, 30 could be crucial targets in the setting of natural bioactive compounds able to limit the cellular oxidative processes responsible for the onset of diabetes and its vascular complications. …”

Section: Discussionmentioning

confidence: 99%

“…7 The enhanced reactive oxygen species (ROS) generation and depletion of nitric oxide (NO) bioavailability alter the endothelium functionality during hyperglycaemia, a key feature of diabetes and its vascular complications. 9,10 The hyperglycaemia-induced endothelial dysfunction is also mediated by downregulation of sirtuins, proteins that take part to the mechanisms regulating vascular dysfunction related to aging, inflammation, and diabetes. 11,12 At vascular level, the effects of sirtuin 1 (SIRT1) are due to the deacetylation of multiple targets, including endothelial nitric oxide synthase, peroxisome proliferator-activated receptor-γ coactivator 1-α, p53, forkhead Box O family, and nuclear factor-kappa B (NF-κB).…”

Section: Introductionmentioning

confidence: 99%

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Gaba-betaine modulates SIRT1 and p16INK4A expression during high-glucose induced endothelial cell senescence

et al. 2017

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Gaba-betaine (γ-aminobutyric acid betaine, GabaBet), a betaine formed by trimethyllysine (TML), is a precursor of the L-carnitine biosynthesis. Betaine, quaternary ammonium compounds, are naturally occurring osmoprotectants or compatible solutes with a widespread distribution in plant and animal kingdoms. Among betaines, stachydrine (N,N-dimethyl-L-proline) (ProBet), abundant in citrus fruit juices, inhibits the deleterious effect of high-glucose (hGluc) on endothelial cells (EC). Hyperglycaemia induces endothelial dysfunction and vascular complications by promoting EC senescence, altering antioxidant enzyme involved in the system defence against reactive oxygen species (ROS), and limiting the cell proliferative potential. This study was designed to determine the possible effect of GabaBet against the hGluc-induced oxidative injury. Evaluation of cell viability revealed that GabaBet does not affect cell proliferation from 0.001 to 1mM up to 72 h. Of interest, co-treatment for 48 h with GabaBet (0.1 mM) and hGluc (30 mM) (GabaBet+hGluc) attenuated the EC growth arrest in the G0/G1 cell cycle phase. GabaBet counteracted the hGluc induced upregulation of p16 INK4A and the increased superoxide dismutase activity. Moreover, the downregulation of sirtuin 1 (SIRT1) expression, occurring under hGluc conditions, is significantly blocked by GabaBet. On the whole, results show that beneficial effects of GabaBet in the prevention of hGluc-induced endothelial senescence is paralleled by the modulation of SIRT1 and p16 INK4A expression levels.

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Ergothioneine – a diet‐derived antioxidant with therapeutic potential

2018

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Ergothioneine is a thiol/thione molecule synthesised only by some fungi and bacteria. Nonetheless, it is avidly taken up from the diet by humans and other animals through a transporter, OCTN1, and accumulates to high levels in certain tissues. Ergothioneine is not rapidly metabolised, or excreted in urine and is present in many, if not all, human tissues and body fluids. Ergothioneine has powerful antioxidant and cytoprotective properties in vitro and there is evidence that the body may concentrate it at sites of tissue injury by raising OCTN1 levels. Decreased blood and/or plasma levels of ergothioneine have been observed in some diseases, suggesting that a deficiency could be relevant to the disease onset or progression. This brief Review explores the possible roles of ergothioneine in human health and disease.

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Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6

Cited by 99 publications

References 46 publications

SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection

SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection

Gaba-betaine modulates SIRT1 and p16INK4A expression during high-glucose induced endothelial cell senescence

Ergothioneine – a diet‐derived antioxidant with therapeutic potential

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