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.

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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