Inhibition of CACNA1H attenuates doxorubicin-induced acute cardiotoxicity by affecting endoplasmic reticulum stress

Hu, Junxia; Wu, Qi; Wang, Zhiwei; Hong, Junmou; Chen, Ruoshi; Li, Bowen; Hu, Zhipeng; Hu, Xiaoping; Zhang, Min

doi:10.1016/j.biopha.2019.109475

Cited by 24 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DOX-induced cardiomyopathy is the most common type of drug-induced heart disease ( 33 ). DOX-induced damage to the heart has significantly limited its therapeutic use in the clinic ( 34 ). The main mechanism of action of DOX is inhibition of DNA double-strand break, DNA replication and DNA transcription by topoisomerase 2 inhibition.…”

Section: Discussionmentioning

confidence: 99%

Catalpol ameliorates doxorubicin‑induced inflammation and oxidative stress in H9C2 cells through PPAR‑γ activation

Jiang

Zhang

2020

Exp Ther Med

View full text Add to dashboard Cite

Drug-induced cardiomyopathy is a severe disease that leads to refractory heart disease at late stages, with increasing detrimental effects. DOX-induced cell damage is primarily induced via cellular oxidative stress. The present study investigated the effects of catalpol on doxorubicin (DOX)-induced H9C2 cardiomyocyte inflammation and oxidative stress. The Cell Counting Kit-8 assay was performed to detect cell viability, and western blotting was performed to detect the expression of peroxisome proliferator-activated receptor (PPAR)-γ in H9C2 cells. The expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 were measured using ELISAs. Furthermore, the oxidative stress kit was used to detect the levels of malondialdehyde, superoxide dismutase and glutathione peroxidase. A reactive oxygen species (ROS) kit and DCF-DA staining were used to detect ROS levels. The results indicated that DOX treatment inhibited H9C2 cell expression of PPAR-γ and decreased H9C2 cell viability. Various concentrations of catalpol exhibited a less potent effect on H9C2 cell viability compared with DOX; however, catalpol increased the viability of DOX-induced H9C2 cells. Catalpol treatment also significantly decreased the expression levels of inflammatory factors (TNF-α, IL-1β and IL-6) in DOX-induced H9C2 cells, which was reversed by transfections with short hairpin RNA targeting PPAR-γ. Results from the present study indicated that catalpol ameliorated DOX-induced inflammation and oxidative stress in H9C2 cardiomyoblasts by activating PPAR-γ.

show abstract

Section: Discussionmentioning

confidence: 99%

Catalpol ameliorates doxorubicin‑induced inflammation and oxidative stress in H9C2 cells through PPAR‑γ activation

Jiang

Zhang

2020

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…CACNA1H was found to be related to DOX-induced cardiac toxicity, while the CACNA1H-specific inhibitor ABT-639 significantly reduced DOX-induced cardiac damage and dysfunction, and relieved ER stress and the apoptosis of cardiac myocytes [ 221 , 222 ]. One study assessed DOX-induced heart damage and changes in CACNA1H expression, and investigated the effects of ER stress and apoptosis on DOX-induced heart damage in mice [ 222 ]. To determine the effect of CACNA1H in this process, this study assessed the DOX-induced changes in heart injury and ER stress after treatment with a CACNA1H-specific inhibitor, ABT-639.…”

Section: Protective Genes In Cancer Treatment-induced Cardiotoxicimentioning

confidence: 99%

Possible Susceptibility Genes for Intervention against Chemotherapy-Induced Cardiotoxicity

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Recent therapeutic advances have significantly improved the short- and long-term survival rates in patients with heart disease and cancer. Survival in cancer patients may, however, be accompanied by disadvantages, namely, increased rates of cardiovascular events. Chemotherapy-related cardiac dysfunction is an important side effect of anticancer therapy. While advances in cancer treatment have increased patient survival, treatments are associated with cardiovascular complications, including heart failure (HF), arrhythmias, cardiac ischemia, valve disease, pericarditis, and fibrosis of the pericardium and myocardium. The molecular mechanisms of cardiotoxicity caused by cancer treatment have not yet been elucidated, and they may be both varied and complex. By identifying the functional genetic variations responsible for this toxicity, we may be able to improve our understanding of the potential mechanisms and pathways of treatment, paving the way for the development of new therapies to target these toxicities. Data from studies on genetic defects and pharmacological interventions have suggested that many molecules, primarily those regulating oxidative stress, inflammation, autophagy, apoptosis, and metabolism, contribute to the pathogenesis of cardiotoxicity induced by cancer treatment. Here, we review the progress of genetic research in illuminating the molecular mechanisms of cancer treatment-mediated cardiotoxicity and provide insights for the research and development of new therapies to treat or even prevent cardiotoxicity in patients undergoing cancer treatment. The current evidence is not clear about the role of pharmacogenomic screening of susceptible genes. Further studies need to done in chemotherapy-induced cardiotoxicity.

show abstract

“…A large number of unfolded or misfolded proteins accumulate in the ER. In order to survive to ER stress, the ER chaperon protein, glucose-regulated protein (GRP78) and other ER chaperones were activated to show protective effects [ 9 , 10 ]. FAM134B plays a crucial role ER autophagy.…”

Section: Introductionmentioning

confidence: 99%

FAM134B-mediated endoplasmic reticulum autophagy protects against sepsis myocardial injury in mice

Chen

et al. 2021

Aging

View full text Add to dashboard Cite

Reticulophagy regulator 1 (RETEG1, also known as FAM134B) plays a crucial role in endoplasmic reticulum autophagy. We aimed to explore the effect of FAM134B-mediated endoplasmic reticulum autophagy in sepsis myocardial injury in mice. Sepsis myocardial injury mice were established via cecal ligation and puncture procedures. The expression of FAM134B and LC3-II/I was determined using immunohistochemistry. Myocardial tissue morphological changes and apoptosis were examined using hematoxylin and eosin (H&E) staining and TUNEL analysis. The effects of FAM134B knockdown or overexpression on mice with sepsis myocardial injury were also studied. The levels of TNF-α, IL-6, IL-8, and IL-10 were evaluated using enzyme-linked immunosorbent assay (ELISA). Autophagy- and apoptosis-related protein expression was detected using western blotting. The effect of FAM134B on Lipopolysaccharide (LPS) -induced cardiomyocytes was also studied. The expression of FAM134B and LC3-II/I increased in sepsis mice and lipopolysaccharide (LPS)-treated cardiomyocytes. 3-Methyladenine (3-MA) significantly inhibited FAM134B and LC3-II/I expression and promoted myocardial injury, inflammation response, and cardiomyocyte apoptosis. The overexpression of FAM134B could minimize myocardial injury, inflammation, and apoptosis, whereas FAM134B knockdown showed opposite effects. FAM134B-mediated endoplasmic reticulum autophagy had a protective effect on sepsis myocardial injury in mice by reducing inflammation and tissue apoptosis, which may provide new insights for sepsis myocardial injury therapies.

show abstract

Inhibition of CACNA1H attenuates doxorubicin-induced acute cardiotoxicity by affecting endoplasmic reticulum stress

Cited by 24 publications

References 33 publications

Catalpol ameliorates doxorubicin‑induced inflammation and oxidative stress in H9C2 cells through PPAR‑γ activation

Catalpol ameliorates doxorubicin‑induced inflammation and oxidative stress in H9C2 cells through PPAR‑γ activation

Possible Susceptibility Genes for Intervention against Chemotherapy-Induced Cardiotoxicity

FAM134B-mediated endoplasmic reticulum autophagy protects against sepsis myocardial injury in mice

Contact Info

Product

Resources

About