Deacetylation-dependent regulation of PARP1 by SIRT2 dictates ubiquitination of PARP1 in oxidative stress-induced vascular injury

Zhang, Naijin; Zhang, Ying; Wu, Boquan; Wu, Shaojun; You, Shilong; Lu, Saien; Liu, Jingwei; Huang, Xinyue; Xu, Jiaqi; Cao, Liu; Sun, Yingxian

doi:10.1016/j.redox.2021.102141

Cited by 32 publications

(21 citation statements)

References 26 publications

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“…These findings suggest that the mechanism by which probiotics alleviate vascular endothelial dysfunction may be related to the inhibition of oxidative stress. Oxidative stress is a crucial factor leading to endothelial dysfunction, including direct damage to the vascular endothelium, induction of inflammation, and oxidation of LDL-C, inhibition of excessive oxidative stress response in vascular endothelium has been proven effective in counteracting the progression of AS [59][60][61]. Some probiotics have been shown to exhibit superior antioxidant capacity.…”

Section: Probiotics Improve Endothelial Dysfunctionmentioning

confidence: 99%

Probiotics Bring New Hope for Atherosclerosis Prevention and Treatment

Zhai

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cardiovascular disease is the leading cause of human mortality and morbidity worldwide. Atherosclerosis (AS) is the underlying pathological responsible in most acute and severe cardiovascular diseases including myocardial infarction and stroke. However, current drugs applied to the treatment of AS are not clinically effective, and there is a large residual risk of cardiovascular disease and multiple side effects. Increasing evidence supports a close relationship between microorganisms and the incidence of AS. Recent data have shown that probiotics can improve multiple key factors involved in the development and progression of AS, including cholesterol metabolism imbalance, endothelial dysfunction, proinflammatory factor production, macrophage polarization, intestinal flora disturbance, and infection with pathogenic microorganisms, and therefore probiotics have attracted great interest as a novel potential “medicine”. This review is aimed at summarizing the effects of probiotics on various influencing factors, and providing valuable insights in the search for early prevention and potential therapeutic strategies for AS.

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Section: Probiotics Improve Endothelial Dysfunctionmentioning

confidence: 99%

Probiotics Bring New Hope for Atherosclerosis Prevention and Treatment

Zhai

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Studies have shown that SIRT2 can also deacetylate PARP1 K249, resulting in the ubiquitination and degradation of PARP1 by WW domain-containing protein 2 (WWP2), thereby alleviating the vascular oxidative stress injury caused by PARP1 mediated by angiotensin II (Ang II) [ 107 ]. Alternatively, SIRT2 can deacetylate K431 of Bcl-2-associated athanogene 3 (BAG3), thereby mediating BAG3 binding to PARP1 to promote the ubiquitination degradation of WWP2 at PARP1 K249 to protect against oxidative damage [ 108 ].…”

Section: Sirt2 and Metabolic Disordersmentioning

confidence: 99%

“…Studies have shown that during atherosclerosis, SIRT2 can inhibit the occurrence and development of atherosclerotic macrophages by inhibiting the polarization of macrophages [ 139 ]. Alternatively, SIRT2 can directly act on its target Nrf2/FOXO3/PARP1 and indirectly act on PARP1 by deacetylating BAG3, which alleviates the further aggravation of hypertension and oxidative stress, prevents intraluminal occlusion and stenosis from causing organic lesions, and avoids the occurrence of coronary heart disease (CHD) of myocardial ischaemia [ 97 , 98 , 107 , 108 ]. Furthermore, in acute myocardial infarction (AMI), functional DNA sequence variants (DSVs) can alter the SIRT2 levels by affecting the transcriptional activity of the SIRT2 promoter, leading to the progression of AMI into severe disease [ 140 ].…”

Section: Role Of Sirt2 In Diseasementioning

confidence: 99%

Multiple Roles of SIRT2 in Regulating Physiological and Pathological Signal Transduction

et al. 2022

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Sirtuin 2 (SIRT2), as a member of the sirtuin family, has representative features of evolutionarily highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase activity. In addition, SIRT2, as the only sirtuin protein colocalized with tubulin in the cytoplasm, has its own functions and characteristics. In recent years, studies have increasingly shown that SIRT2 can participate in the regulation of gene expression and regulate signal transduction in the metabolic pathway mainly through its post-translational modification of target genes; thus, SIRT2 has become a key centre in the metabolic pathway and participates in the pathological process of metabolic disorder-related diseases. In this paper, it is discussed that SIRT2 can regulate all aspects of gene expression, including epigenetic modification, replication, transcription and translation, and post-translational modification, which enables SIRT2 to participate in energy metabolism in life activities, and it is clarified that SIRT2 is involved in metabolic process-specific signal transduction mechanisms. Therefore, SIRT2 can be involved in metabolic disorder-related inflammation and oxidative stress, thereby triggering the occurrence of metabolic disorder-related diseases, such as neurodegenerative diseases, tumours, diabetes, and cardiovascular diseases. Currently, although the role of SIRT2 in some diseases is still controversial, given the multiple roles of SIRT2 in regulating physiological and pathological signal transduction, SIRT2 has become a key target for disease treatment. It is believed that with increasing research, the clinical application of SIRT2 will be promoted.

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“…Therefore, in the vascular milieu of low-grade sterile inflammation, the defense mechanism of sirtuins will be impaired. In particular, sirtuin 2 has been shown to protect against oxidative stress-induced vascular injury by deacetylation and ubiquitination of the oxidative stress injury-related protein poly(ADP-ribose) polymerase 1 (PARP1) in mice [ 64 ]. Besides, one of the mechanisms by which sirtuins mitigate chronic inflammation in the vasculature is the inhibition of the NLRP3 inflammasome [ 65 ].…”

Section: Oxidative Stress and The Nlrp3 Inflammasomementioning

confidence: 99%

NLRP3 Inflammasome in Vascular Disease: A Recurrent Villain to Combat Pharmacologically

et al. 2022

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Despite the great advances in medicine, mortality from cardiovascular diseases keeps on growing. This tendency is not likely to change considering the pandemic proportions of obesity and diabetes. Besides, the global population is more aged as life expectancy increases, and vascular aging plays a key role in the increased risk of vascular disease. In light of recent trials, namely the CANTOS study, showing the enormous potential of anti-inflammatory therapies and in particular those targeted to IL-1β, a change in therapeutical management of cardiovascular diseases is coming about. The NLRP3 inflammasome is a multiprotein complex that assembles to engage the innate immune defense by processing the maturation of pro-inflammatory cytokines IL-1β and IL-18. Substantial evidence has positioned the NLRP3 inflammasome at the center of vascular disease progression, with a particular significance in the context of aging and the low-grade chronic inflammation associated (inflammaging). Therefore, pharmacological blockade of the NLRP3 inflammasome and its end products has arisen as an extremely promising tool to battle vascular disease. In this review, we discuss the mechanisms by which the NLRP3 inflammasome contributes to vascular disease, with particular attention to the consequences of aging, and we enumerate the therapeutic options available to combat this recurrent villain.

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Deacetylation-dependent regulation of PARP1 by SIRT2 dictates ubiquitination of PARP1 in oxidative stress-induced vascular injury

Cited by 32 publications

References 26 publications

Probiotics Bring New Hope for Atherosclerosis Prevention and Treatment

Probiotics Bring New Hope for Atherosclerosis Prevention and Treatment

Multiple Roles of SIRT2 in Regulating Physiological and Pathological Signal Transduction

NLRP3 Inflammasome in Vascular Disease: A Recurrent Villain to Combat Pharmacologically

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