ArticlePloS one2019
CaMKII activation participates in doxorubicin cardiotoxicity and is attenuated by moderate GRP78 overexpression.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Cardiovascular adverse events associated with cyclophosphamide, pegylated liposomal doxorubicin, vincristine, and prednisone with or without rituximab ((R)-CDOP) in non-Hodgkin's lymphoma: A systematic review and meta-analysis.Frontiers in pharmacology · 2022Pooled it
- GRP78 dysregulation: A proposed molecular mechanism linking the tumor microenvironment to sepsis susceptibility in patients with cancer (Review).International journal of molecular medicine · 2026Review
- Persistently increased CaMKIIδ autophosphorylation mediates pathologic SR Ca loss in a murine model of Doxorubicin-induced cardiomyopathy.Journal of molecular and cellular cardiology plus · 2026Article
- The multifaceted mechanisms of Tanshinone IIA in doxorubicin-induced cardiotoxicity.Frontiers in medicine · 2026Review
- Multiscale Imaging of Human Adipose Tissue: A Neglected Partner in Proteinuria Linked to Obesity.Biomedicines · 2025Review
- Mitochondrial Amount Determines Doxorubicin-Induced Cardiotoxicity in Cardiomyocytes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The cardio-oncologic burden of breast cancer: molecular mechanisms and importance of preclinical models.Basic research in cardiology · 2025Review
- Evolution of Theories on Doxorubicin-Induced Late Cardiotoxicity-Role of Topoisomerase.International journal of molecular sciences · 2024Review
- Precision Treatment of Anthracycline-Induced Cardiotoxicity: An Updated Review.Current treatment options in oncology · 2024Review
- Research Progress on Flavonoids in Traditional Chinese Medicine to Counteract Cardiotoxicity Associated with Anti-Tumor Drugs.Reviews in cardiovascular medicine · 2024Review
- Mitochondrial Responses to Sublethal Doxorubicin in H9c2 Cardiomyocytes: The Role of Phosphorylated CaMKII.Yonago acta medica · 2024Article
- Potential role of endoplasmic reticulum stress in doxorubicin-induced cardiotoxicity-an update.Frontiers in pharmacology · 2024Review
- Article
- Cardiac Arrhythmias in Oncological Patients-Epidemiology, Risk Factors, and Management within the Context of the New ESC 2022 Guidelines.Current oncology reports · 2023Review
- Intermittent Hypoxic Preconditioning Plays a Cardioprotective Role in Doxorubicin-Induced Cardiomyopathy.Cardiovascular toxicology · 2023Article
- The Protective Effect of Mangiferin on Formaldehyde-Induced HT22 Cell Damage and Cognitive Impairment.Pharmaceutics · 2023Article
- A RGS7-CaMKII complex drives myocyte-intrinsic and myocyte-extrinsic mechanisms of chemotherapy-induced cardiotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Doxorubicin resistance in breast cancer is mediated via the activation of FABP5/PPARγ and CaMKII signaling pathway.Frontiers in pharmacology · 2023Article
- Understanding the Protective Role of Exosomes in Doxorubicin-Induced Cardiotoxicity.Oxidative medicine and cellular longevity · 2022Review
- Mechanisms and Drug Intervention for Doxorubicin-Induced Cardiotoxicity Based on Mitochondrial Bioenergetics.Oxidative medicine and cellular longevity · 2022Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The clinical use of the chemotherapeutic doxorubicin (Dox) is limited by cardiotoxic side-effects. One of the early Dox effects is induction of a sarcoplasmic reticulum (SR) Ca2+ leak. The chaperone Glucose regulated protein 78 (GRP78) is important for Ca2+ homeostasis in the endoplasmic reticulum (ER)-the organelle corresponding to the SR in non-cardiomyocytes-and has been shown to convey resistance to Dox in certain tumors. Our aim was to investigate the effect of cardiac GRP78 gene transfer on Ca2+ dependent signaling, cell death, cardiac function and survival in clinically relevant in vitro and in vivo models for Dox cardiotoxicity.By using neonatal cardiomyocytes we could demonstrate that Dox induced Ca2+ dependent Ca2+ /calmodulin-dependent protein kinase II (CaMKII) activation is one of the factors involved in Dox cardiotoxicity by promoting apoptosis. Furthermore, we found that adeno-associated virus (AAV) mediated GRP78 overexpression partly protects neonatal cardiomyocytes from Dox induced cell death by modulating Ca2+ dependent pathways like the activation of CaMKII, phospholamban (PLN) and p53 accumulation. Most importantly, cardiac GRP78 gene therapy in mice treated with Dox revealed improved diastolic function (dP/dtmin) and survival after Dox treatment. In conclusion, our results demonstrate for the first time that Ca2+ dependent CaMKII activation fosters Dox cardiomyopathy and provide additional insight into possible mechanisms by which GRP78 overexpression protects cardiomyocytes from Doxorubicin toxicity.
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