Emerging role of SIRT3 in mitochondrial dysfunction and cardiovascular diseases

Wu, Jie; Zeng, Zhenhua; Zhang, Weijin; Deng, Zhenmiao; Wan, Yahui; Zhang, Yaoyuan; An, Sheng; Huang, Qiaobing; Chen, Zhongqing

doi:10.1080/10715762.2018.1549732

Cited by 68 publications

(33 citation statements)

References 87 publications

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“…Inhibition of SIRT3 can lead to defects in mitochondrial function, leading to the development of various cardiovascular diseases. The activation of SIRT3 may represent a promising therapeutic strategy to improve mitochondrial function and treat related cardiovascular diseases (Mihanfar et al, 2018;Wu J. et al, 2019). Gao et al (2020) extracted rhubarb ingredients and cardiac hypertrophy targets based on machine learning and the network pharmacology method, and the optimal componenttarget combination (emodin-SIRT3) was obtained and further functional analysis was carried out on the combination.…”

Section: Sirt3mentioning

confidence: 99%

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

Gao

Pang

et al. 2020

Front. Pharmacol.

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Emodin is a natural occurring anthraquinone derivative isolated from roots and barks of numerous plants, molds, and lichens. It is found to be an active ingredient in different Chinese herbs including Rheum palmatum and Polygonam multiflorum, and it is a pleiotropic molecule with diuretic, vasorelaxant, anti-bacterial, anti-viral, antiulcerogenic, anti-inflammatory, and anti-cancer effects. Moreover, emodin has also been shown to have a wide activity of anti-cardiovascular diseases. It is mainly involved in multiple molecular targets such as inflammatory, anti-apoptosis, anti-hypertrophy, antifibrosis, anti-oxidative damage, abnormal, and excessive proliferation of smooth muscle cells in cardiovascular diseases. As a new type of cardiovascular disease treatment drug, emodin has broad application prospects. However, a large amount of evidences detailing the effect of emodin on many signaling pathways and cellular functions in cardiovascular disease, the overall understanding of its mechanisms of action remains elusive. In addition, by describing the evidence of the effects of emodin in detail, the toxicity and poor oral bioavailability of mice have been continuously discovered. This review aims to describe a timely overview of emodin related to the treatment of cardiovascular disease. The emphasis is to summarize the pharmacological effects of emodin as an anticardiovascular drug, as well as the targets and its potential mechanisms. Furthermore, the treatment of emodin compared with conventional cardiovascular drugs or target inhibitors, the toxicity, pharmacokinetics and derivatives of emodin were discussed.

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Section: Sirt3mentioning

confidence: 99%

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

Gao

Pang

et al. 2020

Front. Pharmacol.

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“…Sirtuin 3 (SIRT3), as one type of histone deacetylases, offers great influence on oxidative stress to regulate inflammation, hypertension, hyperglycaemia and so on . SIRT3 overexpression alleviated oxidative stress and inhibited keratinocytes differentiation .…”

Section: Introductionmentioning

confidence: 99%

SIRT3 deficiency delays diabetic skin wound healing via oxidative stress and necroptosis enhancement

Yang

Meng

et al. 2020

J Cellular Molecular Medi

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Sirtuin 3 (SIRT3) plays a vital role in several dermatological diseases. However, the role and detailed mechanism of SIRT3 in diabetic wound healing are unknown well yet. To explore possible involvement of SIRT3 and necroptosis in diabetic skin wound healing, SIRT3 knockout (KO) mice and 129S1/SvImJ wild‐type (WT) mice were injected with streptozotocin (STZ), and mice skin fibroblasts were exposed to high glucose (HG). It was found that SIRT3 expression decreased in the skin of diabetic patients. SIRT3 deficiency delayed healing rate, reduced blood supply and vascular endothelial growth factor expression, promoted superoxide production, increased malondialdehyde (MDA) levels, decreased total antioxidant capacity (T‐AOC), reduced superoxide dismutase (SOD) activity and aggravated ultrastructure disorder in skin wound of diabetic mice. SIRT3 deficiency inhibited mice skin fibroblasts migration with HG stimulation, which was restored by SIRT3 overexpression. SIRT3 deficiency also suppressed α‐smooth muscle actin (α‐SMA) expression, enhanced superoxide production but decreased mitochondrial membrane potential with HG stimulation after scratch. SIRT3 deficiency further elevated receptor‐interacting protein kinase 3 (RIPK3), RIPK1 and caspase 3 expression both in vitro and in vivo. Collectively, SIRT3 deficiency delayed skin wound healing in diabetes, the mechanism might be related to impaired mitochondria function, enhanced oxidative stress and increased necroptosis. This may provide a novel therapeutic target to accelerate diabetic skin wound healing.

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“…It has been reported that Sirt3 regulates mitochondrial function through the deacetylation of several metabolic and respiratory enzymes [ 31 ]. The role of Sirt3 has been investigated in several diseases, such as Alzheimer's disease [ 32 ], cardiovascular diseases [ 33 ], and renal diseases [ 34 ]. In addition, Sirt3 is involved in the physiological process of aging [ 31 ], and its expression in skeletal muscle was reduced by 50% in elderly individuals compared to young subjects [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Sirtuin 3 Inhibits Airway Epithelial Mitochondrial Oxidative Stress in Cigarette Smoke-Induced COPD

Zhang

Roth

et al. 2020

Oxidative Medicine and Cellular Longevity

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Mitochondrial damage in airway epithelial cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Sirtuin 3 (Sirt3) is a mitochondrial deacetylase regulating mitochondrial function, but its role in the pathogenesis of COPD is still unknown. The aim of the present study was to investigate the effect of Sirt3 on airway epithelial mitochondria in cigarette smoke-induced COPD. Our present study has shown serious airway inflammation, alveolar space enlargement, and mitochondrial damage of the airway epithelium in COPD rats. Compared to the control rats, Sirt3 protein expression was significantly decreased in the airway epithelium and lung tissue homogenate from COPD rats. In airway epithelial cells (BEAS-2B), cigarette smoke extract (CSE) treatment significantly decreased mRNA and protein expression of Sirt3 and manganese superoxide dismutase (MnSOD), as well as MnSOD activity in a concentration and time-dependent manner. Sirt3 siRNA further significantly intensified the decreases in MnSOD expression and activity and aggravated mitochondrial oxidative stress and cell injury when airway epithelial cells were treated with 7.5% CSE. In contrast, Sirt3 overexpression significantly prevented the decrease of MnSOD expression and activity and improved mitochondrial oxidative stress and cell injury in CSE-treated airway epithelial cells. These data suggest that Sirt3 inhibits airway epithelial mitochondrial oxidative stress possibly through the regulation of MnSOD, thereby contributing to the pathogenesis of COPD.

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Emerging role of SIRT3 in mitochondrial dysfunction and cardiovascular diseases

Cited by 68 publications

References 87 publications

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

SIRT3 deficiency delays diabetic skin wound healing via oxidative stress and necroptosis enhancement

Sirtuin 3 Inhibits Airway Epithelial Mitochondrial Oxidative Stress in Cigarette Smoke-Induced COPD

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