Mitochondrial Sirtuins and Doxorubicin-induced Cardiotoxicity

He, Ling; Liu, Fuxiang; Li, Juxiang

doi:10.1007/s12012-020-09626-x

Cited by 40 publications

(18 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sirtuin 3 (SIRT3), localized in the mitochondria, works as a deacetylase of mitochondrial protein [7][8][9]. SIRT3 maintains mitochondrial homeostasis by promoting mitochondrial dynamics, antioxidation, and mitophagy, as well as deacetylation of manganese superoxide dismutase (MnSOD), enhancing its biological activity in senescent NPCs and indicating that SIRT3 might play an important role in normal mitochondrial function in NPCs against oxidative stress [10].…”

Section: Introductionmentioning

confidence: 99%

Promoting Nrf2/Sirt3‐Dependent Mitophagy Suppresses Apoptosis in Nucleus Pulposus Cells and Protects against Intervertebral Disc Degeneration

Zhang

Qian

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

One of the causes of intervertebral disc degeneration (IVDD) is nucleus pulposus cell (NPC) death, possibly apoptosis. In this study, we explored the role of the Nrf2/Sirt3 pathway and tert-butylhydroquinone (t-BHQ) in IVDD and elucidated the potential working mechanism. Reactive oxygen species (ROS) assay kits and malondialdehyde (MDA) assay kits were used to assess oxidative stress. Western blot and TUNEL staining were used to examine apoptosis. After siRNA against Nrf2 or lentivirus against Sirt3 was transfected into NPCs, the mechanism of the effect of the Nrf2/Sirt3 pathway on NPCs was assessed. The interaction between t-BHQ and its potential interacting protein NRF2 was further investigated through protein docking analysis. ChIP examined the binding affinity between Nrf2 and Sirt3 promoter. In vivo experiments, X-ray, hematoxylin-eosin (HE) staining, Safranin O staining, and immunohistochemistry were used to evaluate IVDD grades. The results demonstrated that activation of the Nrf2/Sirt3 pathway inhibited tert-butyl hydroperoxide- (TBHP-) induced apoptosis and mitochondrial dysfunction in vitro. In addition to apoptosis, upregulation of the Nrf2/Sirt3 pathway induced by t-BHQ restored TBHP-induced autophagic flux disturbances. However, its protective effect was reversed by chloroquine and Si-ATG5. Furthermore, t-BHQ ameliorated IVDD development in a rat model. In conclusion, our findings indicate that the Nrf2/Sirt3 pathway and its agonist represent a potential candidate for treating IVDD.

show abstract

Section: Introductionmentioning

confidence: 99%

Promoting Nrf2/Sirt3‐Dependent Mitophagy Suppresses Apoptosis in Nucleus Pulposus Cells and Protects against Intervertebral Disc Degeneration

Zhang

Qian

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…SIRT3 plays an important role in regulating mitochondrial bioenergetics. SIRT3 maintains oxidative phosphorylation via promoting fatty acid oxidation and pyruvate utilization [38]. It also regulates ROS generation at the electron transport chain by increasing the expression/activities of antioxidant enzymes [39,40] and maintains mitochondrial dynamics by targeting OPA1 [41,42].…”

Section: Dox Accumulates In the Mitochondria And Perturbs Mitochondri...mentioning

confidence: 99%

Mitochondrial-Targeted Therapy for Doxorubicin-Induced Cardiotoxicity

Leung

Poon

2022

IJMS

View full text Add to dashboard Cite

Anthracyclines, such as doxorubicin, are effective chemotherapeutic agents for the treatment of cancer, but their clinical use is associated with severe and potentially life-threatening cardiotoxicity. Despite decades of research, treatment options remain limited. The mitochondria is commonly considered to be the main target of doxorubicin and mitochondrial dysfunction is the hallmark of doxorubicin-induced cardiotoxicity. Here, we review the pathogenic mechanisms of doxorubicin-induced cardiotoxicity and present an update on cardioprotective strategies for this disorder. Specifically, we focus on strategies that can protect the mitochondria and cover different therapeutic modalities encompassing small molecules, post-transcriptional regulators, and mitochondrial transfer. We also discuss the shortcomings of existing models of doxorubicin-induced cardiotoxicity and explore advances in the use of human pluripotent stem cell derived cardiomyocytes as a platform to facilitate the identification of novel treatments against this disorder.

show abstract

“…In particular, three sirtuins, SIRT3, SIRT4, and SIRT5 reside inside the mitochondrial matrix where they regulate proteins involved in metabolic reactions, energy production, antioxidant pathways, apoptosis, and autophagy, thus promoting mitochondrial homeostasis (18,19). These targets, including SOD2, FOXO, p53, AMP-activated protein kinase (AMPK), and mammalian target of rapamycin (mTOR) are post-translationally modified by sirtuins, and allow a rapid homeostatic metabolic response to changes in energy expenditure/supply ratio, which occurs in several circumstances, such as calorie restriction (CR), fasting, physical exercise, and metabolic stress (Figure 1) (18,20,21).…”

Section: Mitochondrial Sirtuinsmentioning

confidence: 99%

Redox Homeostasis in Cardiovascular Disease: The Role of Mitochondrial Sirtuins

et al. 2022

View full text Add to dashboard Cite

Cardiovascular disease (CVD) is still the leading cause of death worldwide. Despite successful advances in both pharmacological and lifestyle strategies to fight well-established risk factors, the burden of CVD is still increasing. Therefore, it is necessary to further deepen our knowledge of the pathogenesis of the disease for developing novel therapies to limit even more its related morbidity and mortality. Oxidative stress has been identified as a common trait of several manifestations of CVD and could be a promising target for innovative treatments. Mitochondria are a major source of oxidative stress and sirtuins are a family of enzymes that generate different post-translational protein modifications, thus regulating important cellular processes, including cell cycle, autophagy, gene expression, and others. In particular, three sirtuins, SIRT3, SIRT4, and SIRT5 are located within the mitochondrial matrix where they regulate energy production and antioxidant pathways. Therefore, these sirtuins are strongly involved in the balance between oxidant and antioxidant mechanisms. In this review, we summarize the activities of these sirtuins with a special focus on their role in the control of oxidative stress, in relation to energy metabolism, atherosclerosis, and CVD.

show abstract

Mitochondrial Sirtuins and Doxorubicin-induced Cardiotoxicity

Cited by 40 publications

References 112 publications

Promoting Nrf2/Sirt3‐Dependent Mitophagy Suppresses Apoptosis in Nucleus Pulposus Cells and Protects against Intervertebral Disc Degeneration

Promoting Nrf2/Sirt3‐Dependent Mitophagy Suppresses Apoptosis in Nucleus Pulposus Cells and Protects against Intervertebral Disc Degeneration

Mitochondrial-Targeted Therapy for Doxorubicin-Induced Cardiotoxicity

Redox Homeostasis in Cardiovascular Disease: The Role of Mitochondrial Sirtuins

Contact Info

Product

Resources

About