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CPNE5 overexpression inhibits cardiomyocytes apoptosis by promoting the degradation of FAS receptor

  • 0Department of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
Iscience +

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September 2, 2025

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September 2, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Copine-5 (CPNE5) overexpression protects the heart from damage by reducing cell death and fibrosis. It achieves this by promoting the degradation of FAS via the ER-phagy pathway, safeguarding cardiomyocytes during stress.

Area Of Science

  • Cardiovascular Biology
  • Cellular Signaling
  • Autophagy Research

Background

  • Copine family proteins modulate intracellular signaling.
  • CPNE3 shows cardioprotective effects in ischemia-reperfusion injury.
  • The role of CPNE5 in cardiac pathology is currently unknown.

Purpose Of The Study

  • To investigate the functional role of CPNE5 in cardiac pathology.
  • To determine the effects of CPNE5 overexpression and knockout on cardiac function and injury.
  • To elucidate the molecular mechanisms underlying CPNE5's cardiac effects.

Main Methods

  • Cardiac-specific overexpression and knockout of CPNE5 in mouse models.
  • Assessment of cardiac function, apoptosis, and fibrosis.
  • Analysis of the endoplasmic reticulum-associated degradation (ERAD) and ER-phagy pathways.

Main Results

  • CPNE5 overexpression improved cardiac function, reduced apoptosis and fibrosis in transverse aortic constriction and ischemia-reperfusion models.
  • CPNE5 knockout mice displayed exacerbated cardiac pathology.
  • CPNE5 retains FAS in the endoplasmic reticulum, promoting its degradation via ER-phagy involving LC3 and CALCOCO1.

Conclusions

  • CPNE5 plays a protective role in the heart against ischemic injury and stress.
  • CPNE5 mediates cardioprotection by regulating FAS degradation through the ER-phagy pathway.
  • CPNE5 overexpression protects cardiomyocytes from FASL-induced apoptosis under stress conditions.

Keywords:

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