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Notch1 Protects against Ischemic-Reperfusion Injury by Suppressing PTEN-Pink1-Mediated Mitochondrial Dysfunction and

Qirong Xu1, Sheng Liu2, Qiang Gong2

  • 1Department of Thoracic Surgery, The First Affiliated Hospital, Nanchang University, Nanchang 330006, China.

Cells
|January 8, 2023
PubMed
Abstract

Insights

Notch1 protects against heart injury by inhibiting mitochondrial dysfunction and fragmentation via the PTEN-Pink1 pathway. This finding offers new insights into treating myocardial ischemia/reperfusion injury.

Area of Science:

  • Cardiovascular Research
  • Mitochondrial Biology
  • Cellular Signaling

Background:

  • Myocardial ischemia/reperfusion (I/R) injury contributes to poor outcomes post-heart attack, but its molecular basis is not fully understood.
  • Mitochondrial dysfunction is a key factor in I/R injury, yet the precise mechanisms remain elusive.
  • Previous research indicated Notch1 reduces mitochondrial damage and infarct size.

Purpose of the Study:

  • To investigate the role of Notch1 in regulating mitochondrial function during I/R injury.
  • To elucidate the downstream molecular targets of Notch1 involved in protecting cardiomyocytes.

Main Methods:

  • Established rat I/R and cell hypoxia/reoxygenation models.
  • Quantified PTEN expression using PCR, Western blot, and immunofluorescence.
  • Assessed cell viability (CCK-8), apoptosis (TUNEL), and mitochondrial fission/fusion (MitoTracker Green).
  • Measured cardiac biomarkers (cTnI, LDH, CK) and antioxidant enzymes (SOD) via ELISA.

Main Results:

  • Notch1 inhibited PTEN-Pink1-Parkin signaling in injured cardiomyocytes and hearts, reducing mitochondrial dysfunction and fragmentation.
  • Restoration of PTEN or Pink1 expression significantly diminished the protective effects of Notch1.
  • Notch1 activation suppressed PTEN-mediated mitochondrial fragmentation.

Conclusions:

  • Notch1 activation (N1ICD) provides protection against I/R injury.
  • This protective effect is mediated by the suppression of PTEN-Pink1-dependent mitochondrial dysfunction and fragmentation.
Keywords:
Notch1PTENPink1-Mfn2-Parkinischemic-reperfusion injury

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