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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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PKCδ modulates SP1 mediated mitochondrial autophagy to exacerbate diacetylmorphine-induced ferroptosis in neurons

Mengjie Zhuang1, Sensen Zhu1, Liping Su2

  • 1Xinjiang Medical University, School of Basic Medical Science, Urumqi 830017, China.

International Immunopharmacology
|November 3, 2024
PubMed

Insights

Diacetylmorphine (DA) causes neuronal injury by increasing iron and activating autophagy. Inhibiting protein kinase C delta (PKCδ) and these pathways may protect against DA neurotoxicity.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Diacetylmorphine (DA) is linked to neuronal injury, but mechanisms are unclear.
  • Iron metabolism and autophagy are potential contributors to neurotoxicity.

Purpose of the Study:

  • Investigate the role of iron metabolism and mitochondrial autophagy in DA-induced neurotoxicity.
  • Identify key molecular targets for therapeutic intervention.

Main Methods:

  • Proteomics analysis (TMT) in Sprague-Dawley rats and PC12/SH-SY5Y cells.
  • Assessed protein expression (PKCδ, TFRC, SP1, GPX4, VDAC1, p62, LC3), cellular iron, lipid peroxides, mitochondrial potential, and ROS.
  • Utilized gene silencing and autophagy inhibition techniques.

Main Results:

  • DA upregulated PKCδ, SP1 nuclear translocation, intracellular iron, and lipid peroxides.
  • PKCδ silencing in rats improved behavior and restored GPX4.
  • DA induced mitochondrial autophagy, decreasing mitochondrial membrane potential and increasing ROS, LC3, and decreasing p62.
  • Autophagy inhibition restored mitochondrial function and GPX4/VDAC1 expression.

Conclusions:

  • PKCδ regulates SP1, exacerbating DA-induced neuronal ferroptosis.
  • Inhibiting PKCδ, mitochondrial autophagy, or ferroptosis may mitigate DA neurotoxicity.
Keywords:
DiacetylmorphineMitophagyNeuronal ferroptosisPKCδSP1

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