Honokiol ameliorates radiation-induced brain injury via the activation of SIRT3

Liao, Guixiang; Zhao, Zhihong; Yang, Hai; Li, Xiaming

doi:10.1177/0300060520963993

Cited by 11 publications

(7 citation statements)

References 41 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The protective effects of each pharmacologic agent in diminishing oxidant-induced AEC mtDNA damage parallel our findings using a genetic approach to augment AEC SIRT3 expression [32]. Our observation that honokiol protection against oxidant-induced AEC mtDNA damage occurs in a SIRT3-dependent manner concurs with prior studies showing that honokiol's protective effects are dependent upon SIRT3 in ameliorating murine bleomycin-induced pulmonary fibrosis [37], doxorubicin-induced cardiomyopathy [49], diabetes-induced myocardial dysfunction [51], and radiation-induced brain injury [52]. Although the mechanism by which SIRT3 reduces mtDNA damage was not explored in this study, prior studies have established that SIRT3 can reduce mtROS levels and enhance mtDNA repair in a variety of cell types [24][25][26][27][28][29]32,33,53,54].…”

Section: Discussionsupporting

confidence: 88%

SIRT3 Overexpression Ameliorates Asbestos-Induced Pulmonary Fibrosis, mt-DNA Damage, and Lung Fibrogenic Monocyte Recruitment

Cheresh

Kim

Jablonski

et al. 2021

IJMS

View full text Add to dashboard Cite

Alveolar epithelial cell (AEC) mitochondrial (mt) DNA damage and fibrotic monocyte-derived alveolar macrophages (Mo-AMs) are implicated in the pathobiology of pulmonary fibrosis. We showed that sirtuin 3 (SIRT3), a mitochondrial protein regulating cell fate and aging, is deficient in the AECs of idiopathic pulmonary fibrosis (IPF) patients and that asbestos- and bleomycin-induced lung fibrosis is augmented in Sirt3 knockout (Sirt3−/−) mice associated with AEC mtDNA damage and intrinsic apoptosis. We determined whether whole body transgenic SIRT3 overexpression (Sirt3Tg) protects mice from asbestos-induced pulmonary fibrosis by mitigating lung mtDNA damage and Mo-AM recruitment. Crocidolite asbestos (100 µg/50 µL) or control was instilled intratracheally in C57Bl6 (Wild-Type) mice or Sirt3Tg mice, and at 21 d lung fibrosis (histology, fibrosis score, Sircol assay) and lung Mo-AMs (flow cytometry) were assessed. Compared to controls, Sirt3Tg mice were protected from asbestos-induced pulmonary fibrosis and had diminished lung mtDNA damage and Mo-AM recruitment. Further, pharmacologic SIRT3 inducers (i.e., resveratrol, viniferin, and honokiol) each diminish oxidant-induced AEC mtDNA damage in vitro and, in the case of honokiol, protection occurs in a SIRT3-dependent manner. We reason that SIRT3 preservation of AEC mtDNA is a novel therapeutic focus for managing patients with IPF and other types of pulmonary fibrosis.

show abstract

Section: Discussionsupporting

confidence: 88%

SIRT3 Overexpression Ameliorates Asbestos-Induced Pulmonary Fibrosis, mt-DNA Damage, and Lung Fibrogenic Monocyte Recruitment

Cheresh

Kim

Jablonski

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…SIRT3 resides in the mitochondria and represents a multifunctional deacetylase regulating the acetylation state of the mitochondrial protein involved in MQC [56]. Liao et al [57] found that honokiol treatment increased the ability of SIRT3 to repress the expression of COX-2 and pro-inflammatory cytokines, thus mitigating radiation-induced brain injury in a zebrafish model. SIRT3 deficiency elevated the expression of IL-1β, TNF-α, and COX-2, and increased microglial proliferation and activation [58].…”

Section: Discussionmentioning

confidence: 99%

Targeting Mitochondrial COX-2 Enhances Chemosensitivity via Drp1-Dependent Remodeling of Mitochondrial Dynamics in Hepatocellular Carcinoma

Che

et al. 2022

Cancers

View full text Add to dashboard Cite

Mitochondria are highly dynamic organelles and undergo constant fission and fusion, which are both essential for the maintenance of cell physiological functions. Dysregulation of dynamin-related protein 1 (Drp1)-dependent mitochondrial dynamics is associated with tumorigenesis and the chemotherapeutic response in hepatocellular carcinoma (HCC). The enzyme cyclooxygenase-2 (COX-2) is overexpressed in most cancer types and correlates with a poor prognosis. However, the roles played by the translocation of mitochondrial COX-2 (mito-COX-2) and the interaction between mito-COX-2 and Drp1 in chemotherapeutic responses remain to be elucidated in the context of HCC. Bioinformatics analysis, paired HCC patient specimens, xenograft nude mice, immunofluorescence, transmission electron microscopy, molecular docking, CRISPR/Cas9 gene editing, proximity ligation assay, cytoplasmic and mitochondrial fractions, mitochondrial immunoprecipitation assay, and flow cytometry analysis were performed to evaluate the underlying mechanism of how mito-COX-2 and p-Drp1Ser616 interaction regulates the chemotherapeutic response via mitochondrial dynamics in vitro and in vivo. We found that COX-2 and Drp1 were frequently upregulated and confer a poor prognosis in HCC. We also found that the proportion of mito-COX-2 and p-Drp1Ser616 was increased in HCC cell lines. In vitro, we demonstrated that the enhanced mitochondrial translocation of COX-2 promotes its interaction with p-Drp1Ser616 via PTEN-induced putative kinase 1 (PINK1)-mediated Drp1 phosphorylation activation. This increase was associated with higher colony formation, cell proliferation, and mitochondrial fission. These findings were confirmed by knocking down COX-2 in HCC cells using CRISPR/Cas9 technology. Furthermore, inhibition of Drp1 using pharmacologic inhibitors (Mdivi-1) or RNA interference (siDNM1L) decreased mito-COX-2/p-Drp1Ser616 interaction-mediated mitochondrial fission, and increased apoptosis in HCC cells treated with platinum drugs. Moreover, inhibiting mito-COX-2 acetylation with the natural phytochemical resveratrol resulted in reducing cell proliferation and mitochondrial fission, occurring through upregulation of mitochondrial deacetylase sirtuin 3 (SIRT3), which, in turn, increased the chemosensitivity of HCC to platinum drugs in vitro and in vivo. Our results suggest that targeting interventions to PINK1-mediated mito-COX-2/p-Drp1Ser616-dependent mitochondrial dynamics increases the chemosensitivity of HCC and might help us to understand how to use the SIRT3-modulated mito-COX-2/p-Drp1Ser616 signaling axis to develop an effective clinical intervention in hepatocarcinogenesis.

show abstract

“…Other studies have demonstrated honokiol-mediated SIRT3 activation in vivo in choline-deficient HFD-fed mice [ 168 ] and carbon tetrachloride (CCl4)-stimulated liver-damaged mice [ 169 ] and in cultured primary mouse cardiomyocytes [ 170 ] and AML12 hepatocytes [ 168 ]. Using a zebrafish model of radiation-induced brain injury and HT22 cells, Liao et al observed the neuroprotective effects following honokiol treatment via suppression of ROS, TNF-α, IL-1β, and Cox2, and elevated Sirt3 expression [ 171 ].…”

Section: Translational Significance Of Sirt3 Activationmentioning

confidence: 99%

A Promising Strategy to Treat Neurodegenerative Diseases by SIRT3 Activation

Tyagi

Pugazhenthi

2023

IJMS

View full text Add to dashboard Cite

SIRT3, the primary mitochondrial deacetylase, regulates the functions of mitochondrial proteins including metabolic enzymes and respiratory chain components. Although SIRT3’s functions in peripheral tissues are well established, the significance of its downregulation in neurodegenerative diseases is beginning to emerge. SIRT3 plays a key role in brain energy metabolism and provides substrate flexibility to neurons. It also facilitates metabolic coupling between fuel substrate-producing tissues and fuel-consuming tissues. SIRT3 mediates the health benefits of lifestyle-based modifications such as calorie restriction and exercise. SIRT3 deficiency is associated with metabolic syndrome (MetS), a precondition for diseases including obesity, diabetes, and cardiovascular disease. The pure form of Alzheimer’s disease (AD) is rare, and it has been reported to coexist with these diseases in aging populations. SIRT3 downregulation leads to mitochondrial dysfunction, neuroinflammation, and inflammation, potentially triggering factors of AD pathogenesis. Recent studies have also suggested that SIRT3 may act through multiple pathways to reduce plaque formation in the AD brain. In this review, we give an overview of SIRT3’s roles in brain physiology and pathology and discuss several activators of SIRT3 that can be considered potential therapeutic agents for the treatment of dementia.

show abstract

Honokiol ameliorates radiation-induced brain injury via the activation of SIRT3

Cited by 11 publications

References 41 publications

SIRT3 Overexpression Ameliorates Asbestos-Induced Pulmonary Fibrosis, mt-DNA Damage, and Lung Fibrogenic Monocyte Recruitment

SIRT3 Overexpression Ameliorates Asbestos-Induced Pulmonary Fibrosis, mt-DNA Damage, and Lung Fibrogenic Monocyte Recruitment

Targeting Mitochondrial COX-2 Enhances Chemosensitivity via Drp1-Dependent Remodeling of Mitochondrial Dynamics in Hepatocellular Carcinoma

A Promising Strategy to Treat Neurodegenerative Diseases by SIRT3 Activation

Contact Info

Product

Resources

About