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Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
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Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum

Published on: May 3, 2024

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Proteasome inhibition induces macrophage apoptosis via mitochondrial dysfunction

Jieyan Wang1, Yingling Wang2, Shihan He3

  • 1Department of Urology, The People's Hospital of Longhua, The Affiliated Hospital of Southern Medical University, Shenzhen, Guangdong, China.

Journal of Biochemical and Molecular Toxicology
|August 21, 2021
PubMed

Insights

Proteasome inhibitor MG132 induces macrophage apoptosis via mitochondrial reactive oxygen species (ROS) production and dysfunction. The antioxidant Mito-TEMPO mitigated these effects, highlighting a novel mechanism in macrophage cell death.

Area of Science:

  • Cell Biology
  • Immunology
  • Biochemistry

Background:

  • Dysfunction of the ubiquitin-proteasome system is implicated in various diseases.
  • Proteasome inhibitors like MG132 have antitumor effects and influence inflammatory pathways.
  • The impact of MG132 on macrophage apoptosis was previously unknown.

Purpose of the Study:

  • To investigate the mechanism by which MG132 induces apoptosis in macrophages.
  • To elucidate the role of mitochondrial dysfunction and reactive oxygen species (ROS) in MG132-induced macrophage apoptosis.

Main Methods:

  • Macrophages were treated with MG132, a proteasome inhibitor.
  • Mitochondrial reactive oxygen species (ROS) generation and mitochondrial membrane potential were assessed.
  • Apoptosis was evaluated by measuring the cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP).
  • The effect of the antioxidant Mito-TEMPO on MG132-induced apoptosis was examined.

Main Results:

  • MG132 treatment significantly increased the apoptosis rate in macrophages.
  • MG132 induced mitochondrial ROS generation and loss of mitochondrial membrane potential.
  • Cleavage of caspase-3 and PARP confirmed the induction of apoptosis.
  • Mito-TEMPO attenuated the apoptotic effects of MG132.

Conclusions:

  • Proteasome inhibition by MG132 induces macrophage apoptosis.
  • This process is mediated by the promotion of ROS production and subsequent mitochondrial dysfunction.
  • Targeting ROS may offer a therapeutic strategy in conditions involving proteasome inhibition-induced macrophage apoptosis.
Keywords:
ROSapoptosismitochondrial damageoxidative stressproteasome inhibition

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