2. Academic Validation
  3. Mito-tempo alleviates ox-LDL-provoked foam cell formation by regulating Nrf2/NLRP3 signaling

Mito-tempo alleviates ox-LDL-provoked foam cell formation by regulating Nrf2/NLRP3 signaling

  • Biosci Biotechnol Biochem. 2024 May 8:zbae058. doi: 10.1093/bbb/zbae058.
Zhenyu Huang 1,  Zhaoli Zhou 2 3,  Ying Ma 4,  Yao-Min Hu 4
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Changzheng Hospital of Shanghai, Second Millitary Medical University, Shanghai, China.
  • 2 Shanghai Key Laboratory for Molecular Imaging, Collaborative Scientific Research Center. Shanghai University of Medicine & Health Science, Shanghai, China.
  • 3 Department of Pharmacology, School of Pharmacy, Shanghai University of Medicine & Health Science, Shanghai, China.
  • 4 Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
PMID: 38719485 DOI: 10.1093/bbb/zbae058
Abstract

Our previous studies have demonstrated that Mito-Tempol (also known as 4-hydroxy-Tempo), a mitochondrial Reactive Oxygen Species (ROS) scavenger, alleviates oxidized low-density lipoprotein (ox-LDL)-triggered foam cell formation. Given the effect of oxidative stress on activating the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome, which promotes foam cell formation, we aimed to explore whether Mito-Tempo inhibits ox-LDL-triggered foam cell formation by regulating NLRP3 inflammasome. The results revealed that Mito-Tempo re-activated Nrf2 and alleviated macrophage foam cell formation induced by ox-LDL, whereas the effects were reversed by ML385 (a specific Nrf2 inhibitor). Mito-Tempo restored the expression and nuclear translocation of Nrf2 by decreasing ox-LDL-induced ubiquitination. Furthermore, Mito-Tempo suppressed ox-LDL-triggered NLRP3 inflammasome activation and subsequent Pyroptosis, whereas the changes were blocked by ML385. Mito-Tempo decreased lipoprotein uptake by inhibiting CD36 expression and suppressed foam cell formation by regulating the NLRP3 inflammasome. Taken together, Mito-Tempo exhibits potent anti-atherosclerotic effects by regulating Nrf2/NLRP3 signaling.

Keywords

Mito-Tempo; Nrf2; atherosclerosis; foam cell; macrophage.

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