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

IF 1.3 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioscience, Biotechnology, and Biochemistry Pub Date : 2024-06-21 DOI:10.1093/bbb/zbae058

Zhenyu Huang, Zhaoli Zhou, Ying Ma, Yao-Min Hu

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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.

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线粒体-温度通过调节 Nrf2/NLRP3 信号，缓解氧化-LDL 诱导的泡沫细胞形成。

我们之前的研究表明，线粒体活性氧（ROS）清除剂 Mito-Tempol（又称 4-羟基-Tempo）能缓解氧化低密度脂蛋白（ox-LDL）诱发的泡沫细胞形成。鉴于氧化应激对激活含 NOD-、LRR- 和 pyrin 结构域的 3（NLRP3）炎性小体（NLRP3）有促进泡沫细胞形成的作用，我们旨在探讨米托-天宝是否能通过调节 NLRP3 炎性小体抑制氧化-LDL 触发的泡沫细胞形成。结果发现，米托-天宝能重新激活Nrf2，缓解氧化-LDL诱导的巨噬细胞泡沫细胞形成，而ML385（一种特异性Nrf2抑制剂）则能逆转这种效应。Mito-Tempo 通过减少 ox-LDL 诱导的泛素化，恢复了 Nrf2 的表达和核转位。此外，Mito-Tempo 还抑制了氧化-LDL 触发的 NLRP3 炎症小体活化和随后的脓毒症，而 ML385 则阻止了这些变化。Mito-Tempo 通过抑制 CD36 的表达减少脂蛋白的摄取，并通过调节 NLRP3 炎性体抑制泡沫细胞的形成。综上所述，Mito-Tempo 可通过调节 Nrf2/NLRP3 信号传导，显示出强大的抗动脉粥样硬化作用。

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来源期刊

Bioscience, Biotechnology, and Biochemistry 生物-生化与分子生物学

CiteScore

3.50

自引率

0.00%

发文量

183

审稿时长

1 months

期刊介绍： Bioscience, Biotechnology, and Biochemistry publishes high-quality papers providing chemical and biological analyses of vital phenomena exhibited by animals, plants, and microorganisms, the chemical structures and functions of their products, and related matters. The Journal plays a major role in communicating to a global audience outstanding basic and applied research in all fields subsumed by the Japan Society for Bioscience, Biotechnology, and Agrochemistry (JSBBA).