| Autor: |
Qian Zhang, Piao Luo, Fei Xia, Huan Tang, Jiayun Chen, Junzhe Zhang, Dandan Liu, Yongping Zhu, Yanqing Liu, Liwei Gu, Liuhai Zheng, Zhijie Li, Fan Yang, Lingyun Dai, Fulong Liao, Chengchao Xu, Jigang Wang |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Cell chemical biology. 29(8) |
| ISSN: |
2451-9448 |
| Popis: |
Sepsis is a systemic inflammatory response syndrome with high mortality and morbidity worldwide. In this study, we demonstrate that capsaicin not only suppresses inflammation in lipopolysaccharide (LPS)-induced macrophages, but also effectively inhibits endotoxemia or sepsis-related inflammation in vivo. We have designed and synthesized a series of capsaicin-based probes, which permit the profiling of the target proteins of capsaicin using activity-based protein profiling (ABPP). Among the identified protein targets, we discover that capsaicin directly binds to and inhibits PKM2 and LDHA, and further suppresses the Warburg effect in inflammatory macrophages. Moreover, capsaicin targets COX-2 and downregulates its expression in vivo and in vitro. Taken together, the present findings indicate that capsaicin alleviates the inflammation response and the Warburg effect in a TRPV1-independent manner by targeting PKM2-LDHA and COX-2 in sepsis. Thus, capsaicin may function as a novel agent for sepsis and inflammation treatment. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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