Inhibition of glycogen synthase kinase 3beta ameliorates triptolide-induced acute cardiac injury by desensitizing mitochondrial permeability transition

Wang, Wenwen; Yang, Yanqin; Zhang, Xiong; Kong, Jinliang; Fu, Xinlu; Shen, Feihai; Huang, Zhiying

doi:10.1016/j.taap.2016.10.007

Cited by 22 publications

(12 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been demonstrated that selective inhibition of GSK-3β by SB216763 may significantly ameliorate the adverse effects of triptolide in H9c2 cells through inhibition of CyP-D phosphorylation and modulation of Bcl-2 family proteins, leading to desensitization of mPTP and prevention of mitochondrial apoptosis [85]. Formononetin, a natural isoflavone from Radix Astragali , has been reported to activate Akt/GSK-3β signaling in H9c2 cells.…”

Section: Natural Compounds Regulate Mitochondrial Activity Through Gsmentioning

confidence: 99%

The Key Roles of GSK-3β in Regulating Mitochondrial Activity

Yang

Chen

Gao

et al. 2017

Cell Physiol Biochem

177

119

View full text Add to dashboard Cite

Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, has been reported to show essential roles in molecular pathophysiology of many diseases. Mitochondrion is a dynamic organelle for producing cellular energy and determining cell fates. Stress-induced translocated GSK-3β may interact with mitochondrial proteins, including PI3K-Akt, PGC-1α, HK II, PKCε, components of respiratory chain, and subunits of mPTP. Mitochondrial pool of GSK-3β has been implicated in mediation of mitochondrial functions. GSK-3β exhibits the regulatory effects on mitochondrial biogenesis, mitochondrial bioenergetics, mitochondrial permeability, mitochondrial motility, and mitochondrial apoptosis. The versatile functions of GSK-3β might be associated with its wide range of substrates. Accumulative evidence demonstrates that GSK-3β inactivation may be potentially developed as the promising strategy in management of many diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Intensive efforts have been made for exploring GSK-3β inhibitors. Natural products provide us a great source for screening new lead compounds in inactivation of GSK-3β. The key roles of GSK-3β in mediation of mitochondrial functions are discussed in this review.

show abstract

Section: Natural Compounds Regulate Mitochondrial Activity Through Gsmentioning

confidence: 99%

The Key Roles of GSK-3β in Regulating Mitochondrial Activity

Yang

Chen

Gao

et al. 2017

Cell Physiol Biochem

177

119

View full text Add to dashboard Cite

show abstract

“…There is an increasing number of evidence indicating that GSK-3β is involved in oxidative stress in the relevant brain regions [13–15]. Furthermore, previous studies have suggested SB 216763, an inhibitor of GSK-3β, protects cardiomyocytes from triptolide-induced toxicity by desensitizing mitochondrial permeability transition [16]. A recent study demonstrated that increasing phosphorylation levels of GSK-3β (p-GSK-3β) at its Ser9 could enhance the interaction between adenine nucleotide translocator (ANT) and p-GSK-3β, subsequently inhibiting mitochondrial permeability transition pore (mPTP) opening, reducing mitochondrial superoxide production and preventing neuronal apoptosis [17].…”

Section: Introductionmentioning

confidence: 99%

Grape seed proanthocyanidins ameliorate neuronal oxidative damage by inhibiting GSK-3β-dependent mitochondrial permeability transition pore opening in an experimental model of sporadic Alzheimer’s disease

Sun

Jia

et al. 2019

Aging

View full text Add to dashboard Cite

Mitochondria-associated oxidative stress plays a crucial role in Alzheimer’s disease (AD). Grape seed proanthocyanidins (GSPs) have been reported to prevent oxidative stress. In this study, we investigated the underlying mechanisms of GSPs in protecting neurons against oxidative injury in an experimental model of sporadic AD. Primary mouse cortical neurons were subjected to streptozotocin (STZ) to mimic neuronal oxidative damage in vitro , and mice were subjected to intracerebroventricular (ICV) injection of STZ as an in vivo sporadic AD model. GSPs not only significantly ameliorated neuron loss and mitochondrial dysfunction in mouse cortical neurons pretreated of STZ, but also reduced cognitive impairments, apoptosis and mitochondrial oxidative stress in the cerebral cortex and hippocampus of sporadic AD mice. Moreover, GSPs increased phosphorylation levels of phosphatidylinositol 3-kinase (PI3K), Akt and glycogen synthase kinase 3β (GSK-3β) at its Ser9. Notably, GSPs inhibited STZ-induced mitochondrial permeability transition pore (mPTP) opening via enhancing phosphorylated GSK-3β (p-GSK-3β) binds to adenine nucleotide translocator (ANT), thereby reducing the formation of the complex ANT-cyclophilin D (CypD). In conclusion, GSPs ameliorate neuronal oxidative damage and cognitive impairment by inhibiting GSK-3β-dependent mPTP opening in AD. Our study provides new insights into that GSPs may be a new therapeutic candidate for treatment of AD.

show abstract

“…Experiments in vivo and in vitro showed that triptolide permeabilized the outer mitochondrial membrane and promoted the opening of mPTP, thereby causing mitochondrial dysfunction and apoptosis (Wang et al, 2016b;Xi et al, 2018). In addition, CMM that has cardiotoxicity can also indirectly damage myocardial mitochondria by regulating mitochondrial outer membrane integrity, mitochondrial dynamics, mitochondria-dependent apoptosis genes, and proteins.…”

Section: Mitochondrial Toxicitymentioning

confidence: 99%

Risk Compounds, Preclinical Toxicity Evaluation, and Potential Mechanisms of Chinese Materia Medica–Induced Cardiotoxicity

Zhou

Cao

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Chinese materia medica (CMM) has been applied for the prevention and treatment of diseases for thousands of years. However, arrhythmia, myocardial ischemia, heart failure, and other cardiac adverse reactions during CMM application were gradually reported. CMM-induced cardiotoxicity has aroused widespread attention. Our review aimed to summarize the risk compounds, preclinical toxicity evaluation, and potential mechanisms of CMM-induced cardiotoxicity. All relevant articles published on the PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases for the latest twenty years were searched and manually extracted. The risk substances of CMM-induced cardiotoxicity are relatively complex. A single CMM usually contains various risk compounds, and the same risk substance may exist in various CMM. The active and risk substances in CMM may be transformed into each other under different conditions, such as drug dosage, medication methods, and body status. Generally, the risk compounds of CMM-induced cardiotoxicity can be classified into alkaloids, terpenoids, steroids, heavy metals, organic acids, toxic proteins, and peptides. Traditional evaluation methods of chemical drug-induced cardiotoxicity primarily include cardiac function monitoring, endomyocardial biopsy, myocardial zymogram, and biomarker determination. In the preclinical stage, CMM-induced cardiotoxicity should be systematically evaluated at the overall, tissue, cellular, and molecular levels, including cardiac function, histopathology, cytology, myocardial zymogram, and biomarkers. Thanks to the development of systematic biology, the higher specificity and sensitivity of biomarkers, such as genes, proteins, and metabolic small molecules, are gradually applied for evaluating CMM-induced cardiotoxicity. Previous studies on the mechanisms of CMM-induced cardiotoxicity focused on a single drug, monomer or components of CMM. The interaction among ion homeostasis (sodium, potassium, and calcium ions), oxidative damage, mitochondrial injury, apoptosis and autophagy, and metabolic disturbance is involved in CMM-induced cardiotoxicity. Clarification on the risk compounds, preclinical toxicity evaluation, and potential mechanisms of CMM-induced cardiotoxicity must be beneficial to guide new CMM development and post-marketed CMM reevaluation.

show abstract

Inhibition of glycogen synthase kinase 3beta ameliorates triptolide-induced acute cardiac injury by desensitizing mitochondrial permeability transition

Cited by 22 publications

References 24 publications

The Key Roles of GSK-3β in Regulating Mitochondrial Activity

The Key Roles of GSK-3β in Regulating Mitochondrial Activity

Grape seed proanthocyanidins ameliorate neuronal oxidative damage by inhibiting GSK-3β-dependent mitochondrial permeability transition pore opening in an experimental model of sporadic Alzheimer’s disease

Risk Compounds, Preclinical Toxicity Evaluation, and Potential Mechanisms of Chinese Materia Medica–Induced Cardiotoxicity

Contact Info

Product

Resources

About