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| 標題: | Coenzyme Q0 Inhibits NLRP3 Inflammasome Activation through Mitophagy Induction in LPS/ATP-Stimulated Macrophages |
| 作者: | Hseu, You-Cheng
Tseng, Yu-Fang
Pandey, Sudhir
Shrestha, Sirjana
Lin, Kai-Yuan
Lin, Cheng-Wen
Lee, Chuan-Chen
Huang, Sheng-Teng
Yang, Hsin-Ling |
| 貢獻者: | China Medical University Taiwan
Asia University Taiwan
China Medical University Taiwan
China Medical University Taiwan
China Medical University Taiwan
Chi Mei Hospital
Department of Biotechnology, Chia Nan University of Pharmacy & Science
China Medical University Taiwan
China Medical University Taiwan
China Medical University Hospital - Taiwan |
| 關鍵字: | oxidative stress
cell-death
signal-transduction
down-regulation
ros generation
kappa-b
autophagy
mitochondria
cancer
apoptosis |
| 日期: | 2022 |
| 上傳時間: | 2023-12-11 14:04:21 (UTC+8) |
| 出版者: | HINDAWI LTD |
| 摘要: | Coenzyme Q (CoQ) analogs with a variable number of isoprenoid units have exhibited as anti-inflammatory as well as antioxidant molecules. Using novel quinone derivative CoQ(0) (2,3-dimethoxy-5-methyl-1,4-benzoquinone, zero side chain isoprenoid), we studied its molecular activities against LPS/ATP-induced inflammation and redox imbalance in murine RAW264.7 macrophages. CoQ(0)'s non- or subcytotoxic concentration suppressed the NLRP3 inflammasome and procaspase-1 activation, followed by downregulation of IL1 beta expression in LPS/ATP-stimulated RAW264.7 macrophages. Similarly, treatment of CoQ(0) led to LC3-I/II accumulation and p62/SQSTM1 activation. An increase in the Beclin-1/Bcl-2 ratio and a decrease in the expression of phosphorylated PI3K/AKT, p70 S6 kinase, and mTOR showed that autophagy was activated. Besides, CoQ(0) increased Parkin protein to recruit damaged mitochondria and induced mitophagy in LPS/ATP-stimulated RAW264.7 macrophages. CoQ(0) inhibited LPS/ATP-stimulated ROS generation in RAW264.7 macrophages. Notably, when LPS/ATP-stimulated RAW264.7 macrophages were treated with CoQ(0), Mito-TEMPO (a mitochondrial ROS inhibitor), or N-acetylcysteine (NAC, a ROS inhibitor), there was a significant reduction of LPS/ATP-stimulated NLRP3 inflammasome activation and IL1 beta expression. Interestingly, treatment with CoQ(0) or Mito-TEMPO, but not NAC, significantly increased LPS/ATP-induced LC3-II accumulation indicating that mitophagy plays a key role in the regulation of CoQ(0)-inhibited NLRP3 inflammasome activation. Nrf2 knockdown significantly decreased IL1 beta expression in LPS/ATP-stimulated RAW264.7 macrophages suggesting that CoQ(0) inhibited ROS-mediated NLRP3 inflammasome activation and IL1 beta expression was suppressed due to the Nrf2 activation. Hence, this study showed that CoQ(0) might be a promising candidate for the therapeutics of inflammatory disorders due to its effective anti-inflammatory as well as antioxidant properties. |
| 關聯: | Oxidative Medicine and Cellular Longevity, v.2022, Article ID 4266214 |
| 顯示於類別: | [生物科技系(所)] 期刊論文
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