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Updated: Feb 16, 2026

High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers
Published on: March 24, 2023
Creatine phosphate disodium salt protects against Dox-induced cardiotoxicity by increasing calumenin
Yu Wang1,2, Ying Sun3, Xin Guo1,2
1Inner Mongolia University for the Nationalities, No. 22 Holin He Street, Tongliao, 028002, Inner Mongolia, People's Republic of China.
Abstract:
Inhibiting endoplasmic reticulum stress (ERS)-induced apoptosis may be a new therapeutic target in cardiovascular diseases. Creatine phosphate disodium salt (CP) has been reported to have cardiovascular protective effect, but its effects on ERS are unknown. The aim of this study was to identify the mechanism by which CP exerts its cardioprotection in doxorubicin (Dox)-induced cardiomyocytes injury. In our study, neonatal rats cardiomyocytes (NRC) was randomly divided into control group, model group, and treatment group. The cell viability and apoptosis were detected. grp78, grp94, and calumenin of the each group were monitored. To investigate the role of calumenin, Dox-induced ERS was compared in control and down-regulated calumenin cardiomyocytes. Our results showed that CP decreased Dox-induced apoptosis and relieved ERS. We found calumenin increased in Dox-induced apoptosis with CP. ERS effector C/EBP homologous protein was down-regulated by CP and it was influenced by calumenin. CP could protect NRC by inhibiting ERS, this mechanisms may be associated with its increasing of calumenin.
Insights
Creatine phosphate disodium salt (CP) protects heart cells from injury by reducing endoplasmic reticulum stress (ERS)-induced apoptosis. This cardioprotective effect may involve CP increasing calumenin levels.
Area of Science:
- Cardiovascular Biology
- Cellular Stress Response
- Pharmacology
Background:
- Endoplasmic reticulum stress (ERS)-induced apoptosis is a potential therapeutic target for cardiovascular diseases.
- Creatine phosphate disodium salt (CP) exhibits cardioprotective effects, but its impact on ERS is not well understood.
Purpose of the Study:
- To elucidate the mechanism of CP's cardioprotection against doxorubicin (Dox)-induced cardiomyocyte injury.
- To investigate the role of ERS and calumenin in CP's protective effects.
Main Methods:
- Neonatal rat cardiomyocytes (NRC) were subjected to Dox-induced injury and treated with CP.
- Cell viability, apoptosis, and expression of ERS markers (grp78, grp94, calumenin, C/EBP homologous protein) were assessed.
- The function of calumenin was evaluated by down-regulating its expression.
Main Results:
- CP treatment reduced Dox-induced apoptosis and alleviated ERS in NRC.
- CP treatment led to an increase in calumenin expression under Dox-induced stress.
- CP down-regulated the ERS effector C/EBP homologous protein, an effect influenced by calumenin levels.
Conclusions:
- CP exerts cardioprotection by inhibiting ERS-induced apoptosis in cardiomyocytes.
- The mechanism of CP's protective effect may be associated with its ability to increase calumenin expression.
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