分解代谢
炎症体
上睑下垂
脂多糖
酪氨酸
酪氨酸转氨酶
炎症
药理学
败血症
化学
生物化学
医学
新陈代谢
内分泌学
免疫学
酶
酶诱导剂
作者
Yijun Wei,Mengnan Liu,Jun Han,Haohan Huang,Sheng Xu,Shenghan Zhang,Qiyue Jing,Hanying Wang,Huimin Bu,Yanbo Kou,Zhuanzhuan Liu,Kuiyang Zheng,Yugang Wang
标识
DOI:10.1016/j.intimp.2022.109098
摘要
The metabolic alterations of amino acid metabolism are closely associated with inflammatory response. However, relatively little is known about the roles of phenylalanine (Phe)/tyrosine (Tyr) catabolites during inflammation. Nitisinone (NTBC) is an orphan drug used to treat hereditary tyrosinemia type I potentially by changing Phe/Tyr metabolic flow. In this study, we used NTBC as a tool to investigate the potential role of the Phe/Tyr catabolic pathway in inflammatory responses. We found that NTBC was effective in tempering the bacterial endotoxin lipopolysaccharide (LPS)-induced septic shock in mice. Mechanistically, the protective effect was related to the accumulation of a Phe/Tyr catabolic intermediate, 4-hydroxyphenylpyruvate (4-HPP), induced by the NTBC treatment. 4-HPP could inhibit NLRP3 inflammasome priming and activation processes and therefore reduce IL-1β release and pyroptosis. Like NTBC, 4-HPP was also effective in attenuating endotoxic shock in mice. Our results suggest the Phe/Tyr catabolic pathway as a potential immunoregulatory hub that may be exploited therapeutically to alleviate inflammation.
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