The role of SIRT2 in vascular‐related and heart‐related diseases: A review

Wu, Boquan; You, Shilong; Hao, Qian; Wu, Shaojun; Lu, Saien; Zhang, Ying; Sun, Yingxian; Zhang, Naijin

doi:10.1111/jcmm.16618

Cited by 24 publications

(10 citation statements)

References 101 publications

(163 reference statements)

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“…In this research, we found that IBC-induced S-phase arrest of the breast cancer cells cycle was abrogated by the antioxidant NAC, indicating that the inhibitory effects of IBC on breast cancer cells are ROS-dependent. Studies show that SIRT2 can reduce ROS levels, which is a novel strategy for the treatment of diabetic cardiomyopathy (Wu et al, 2021). In addition, another study showed that the SIRT2 inhibitor TM significantly increased ROS levels in cholangiocarcinoma cells (Xu et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti‐triple‐negative breast cancer efficacy in vitro and in vivo

Ren,

Lei,

Zhang

et al. 2024

Phytotherapy Research

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Triple‐negative breast cancer (TNBC) is the most aggressive and lethal clinical subtype and lacks effective targeted therapies at present. Isobavachalcone (IBC), the main active component of Psoralea corylifolia L., has potential anticancer effects. Herein, we identified IBC as a natural sirtuin 2 (SIRT2) inhibitor and characterized the potential mechanisms underlying the inhibition of TNBC. Molecular dynamics analysis, enzyme activity assay, and cellular thermal shift assay were performed to evaluate the combination of IBC and SIRT2. The therapeutic effects, mechanism, and safety of IBC were analyzed in vitro and in vivo using cellular and xenograft models. IBC effectively inhibited SIRT2 enzyme activity with an IC50 value of 0.84 ± 0.22 μM by forming hydrogen bonds with VAL233 and ALA135 within its catalytic domain. In the cellular environment, IBC bound to and stabilized SIRT2, consequently inhibiting cellular proliferation and migration, and inducing apoptosis and cell cycle arrest by disrupting the SIRT2/α‐tubulin interaction and inhibiting the downstream Snail/MMP and STAT3/c‐Myc pathways. In the in vivo model, 30 mg/kg IBC markedly inhibited tumor growth by targeting the SIRT2/α‐tubulin interaction. Furthermore, IBC exerted its effects by inducing apoptosis in tumor tissues and was well‐tolerated. IBC alleviated TNBC by targeting SIRT2 and triggering the reactive oxygen species ROS/β‐catenin/CDK2 axis. It is a promising natural lead compound for future development of SIRT2‐targeting drugs.

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Section: Discussionmentioning

confidence: 99%

Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti‐triple‐negative breast cancer efficacy in vitro and in vivo

Ren,

Lei,

Zhang

et al. 2024

Phytotherapy Research

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“…Sirt2 is an NAD+-dependent deacetylase that is widely involved in cell division, angiogenesis [48][49][50] , energy metabolism [51] and neurodegenerative [52,53] , cardiovascular disease [54,55] , oxidative stress [56] and many cancers [57,58] , etc. Studies have found that Sirt2 was the most abundant sirtuin expressed in mammalian CNS, especially in cortex, striatum, hippocampus, and spinal cord, suggesting that it might have a role in CNS [59] .…”

Section: Discussionmentioning

confidence: 99%

Label-free quantitative proteomics analyses of mouse astrocytes provides insight into the host response mechanism at different developmental stages ofToxoplasma gondii

Xie

Zhao

et al. 2023

Preprint

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Toxoplasma gondii (T. gondii) is an opportunistic parasite that can infect the central nervous system (CNS), causing severe toxoplasmosis and behavioral cognitive impairment. Mortality is high in immunocompromised individuals with toxoplasmosis, most commonly due to reactivation of infection in the CNS. There are still no effective vaccines and drugs for the prevention and treatment of toxoplasmosis. There are five developmental stages for T. gondii to complete life cycle, of which the tachyzoite and bradyzoite stages are the key to the acute and chronic infection. In this study, to better understanding of how T. gondii interacts with the host CNS at different stages of infection, we constructed acute and chronic infection models of T. gondii in astrocytes, and used label-free proteomics to detect the proteome changes before and after infection, respectively. A total of 4676 proteins were identified, among which 163 differentially expressed proteins (DEPs) (fold change≥1.5 or ≤0.67 and p-value≤0.05) including 109 up-regulated proteins and 54 down-regulated proteins in C8-TA vs C8 group, and 719 DEPs including 495 up-regulated proteins and 224 down-regulated proteins in C8-BR vs C8-TA group. After T. gondii tachyzoites infected astrocytes, DEPs were enriched in immune-related biological processes to promote the formation of bradyzoites and maintain the balance of T. gondii, CNS and brain. After T. gondii bradyzoites infected astrocytes, the DEPs up-regulated the host's glucose metabolism, and some up-regulated DEPs were closely related to neurodegenerative diseases. These findings not only provide new insights into the psychiatric pathogenesis of T. gondii, but also provide potential targets for the treatment of acute and chronic Toxoplasmosis.

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“…[57] Additionally, SIRT2 plays a crucial role in vascular diseases, with its effects on endothelial cell damage dependent on the degree of oxidative stress. [58] Yu et al [59] found that the mRNA and protein levels of SIRT2 were increased in rat cardiomyocytes after short-term CR. Notably, in aortic smooth muscle cells treated with resveratrol, a compound that mimics the effects of CR, SIRT1, SIRT3, and SIRT4 expression was upregulated, while SIRT6 was downregulated, and SIRT2 expression remained unaltered.…”

Section: Potential Mechanisms Linking Cr Cvds and Sirtuinsmentioning

confidence: 99%

Caloric restriction, Sirtuins, and cardiovascular diseases

Wei,

Yang,

Wang

et al. 2024

Chinese Medical Journal

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Caloric restriction (CR) is a well-established dietary intervention known to extend healthy lifespan and exert positive effects on aging-related diseases, including cardiovascular conditions. Sirtuins, a family of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, have emerged as key regulators of cellular metabolism, stress responses, and the aging process, serving as energy status sensors in response to CR. However, the mechanism through which CR regulates Sirtuin function to ameliorate cardiovascular disease remains unclear. In this review, we provide an overview of recent research investigating the interplay between Sirtuins and CR, specifically focusing on their potential implications for cardiovascular health. We provide a comprehensive summary of the benefits of CR for the cardiovascular system mediated directly via Sirtuins. CR has also been shown to have considerable impact on specific metabolic organs, leading to the production of small molecules that enter systemic circulation and subsequently regulate Sirtuin activity within the cardiovascular system. The direct and indirect effects of CR offer a potential mechanism for Sirtuin modulation and subsequent cardiovascular protection. Understanding the interplay between CR and Sirtuins will provide new insights for the development of interventions to prevent and treat cardiovascular diseases.

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The role of SIRT2 in vascular‐related and heart‐related diseases: A review

Cited by 24 publications

References 101 publications

Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti‐triple‐negative breast cancer efficacy in vitro and in vivo

Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti‐triple‐negative breast cancer efficacy in vitro and in vivo

Label-free quantitative proteomics analyses of mouse astrocytes provides insight into the host response mechanism at different developmental stages ofToxoplasma gondii

Caloric restriction, Sirtuins, and cardiovascular diseases

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