Rnd3 protects against doxorubicin-induced cardiotoxicity through inhibition of PANoptosis in a Rock1/Drp1/mitochondrial fission-dependent manner
2025

Rnd3 Protects Against Doxorubicin-Induced Heart Damage

Sample size: 12 publication 10 minutes Evidence: high

Author Information

Author(s): Ge Wen, Zhang Xiaohua, Lin Jie, Wang Yangyang, Zhang Xiao, Duan Yu, Dai Xinchun, Zhang Jiye, Zhang Yan, Jiang Mengyuan, Qiang Huanhuan, Zhao Zhijing, Zhang Xuebin, Sun Dongdong

Primary Institution: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi China

Hypothesis

Rnd3 may serve as a critical pathogenic factor in doxorubicin-induced cardiotoxicity (DIC).

Conclusion

Rnd3 enhances cardiac resilience against doxorubicin-induced cardiotoxicity by stabilizing mitochondrial dynamics and reducing PANoptosis.

Supporting Evidence

  • Rnd3 expression is significantly downregulated in doxorubicin-treated mice.
  • Rnd3 overexpression improves cardiac function and reduces cardiac enzyme levels in doxorubicin-treated mice.
  • Rnd3 inhibits mitochondrial fission by reducing Drp1 phosphorylation.
  • Rnd3 reduces PANoptosis in cardiomyocytes exposed to doxorubicin.

Takeaway

This study shows that a protein called Rnd3 helps protect the heart from damage caused by a cancer drug called doxorubicin by keeping the tiny powerhouses in cells, called mitochondria, healthy.

Methodology

The study used cardiomyocyte-specific Rnd3 transgenic mice and in vitro experiments with adenoviruses to assess the effects of Rnd3 on doxorubicin-induced cardiotoxicity.

Participant Demographics

Male mice were used in the experiments.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1038/s41419-024-07322-0

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication