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- Title
Mito-Tempo alleviates ox-LDL-provoked foam cell formation by regulating Nrf2/NLRP3 signaling.
- Authors
Huang, Zhenyu; Zhou, Zhaoli; Ma, Ying; Hu, Yao-Min
- Abstract
Our previous studies have demonstrated that Mito-Tempol (also known as 4-hydroxy-Tempo), a mitochondrial reactive oxygen species 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.
- Subjects
FOAM cells; LOW density lipoproteins; REACTIVE oxygen species; PYRIN (Protein); NLRP3 protein
- Publication
Bioscience, Biotechnology & Biochemistry, 2024, Vol 88, Issue 7, p759
- ISSN
0916-8451
- Publication type
Article
- DOI
10.1093/bbb/zbae058