دورية أكاديمية
PKM2 regulates the Warburg effect and promotes HMGB1 release in sepsis
| العنوان: | PKM2 regulates the Warburg effect and promotes HMGB1 release in sepsis |
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| المؤلفون: | Yang, L. C., Xie, M., Yang, M. H., Yu, Y., Zhu, S., Lotze, M. T., Billiar, T. R., Wang, H. C., Cao, L. Z., Tang, D. L., +2 additional authors |
| المصدر: | Journal Articles |
| بيانات النشر: | Donald and Barbara Zucker School of Medicine Academic Works |
| سنة النشر: | 2014 |
| المجموعة: | Hofstra Northwell Academic Works (Hofstra Northwell School of Medicine) |
| مصطلحات موضوعية: | HYPOXIA-INDUCIBLE FACTOR-1, MOBILITY GROUP BOX, HISTONE DEACETYLASE, ACTIVITY, CHROMATIN PROTEIN HMGB1, PYRUVATE-KINASE, SEPTIC SHOCK, GLYCOLYTIC METABOLISM, CELL-METABOLISM, BLOOD LACTATE, LATE MEDIATOR, Multidisciplinary Sciences, Emergency Medicine |
| الوصف: | Increasing evidence suggests the important role of metabolic reprogramming in the regulation of the innate inflammatory response, but the underlying mechanism remains unclear. Here we provide evidence to support a novel role for the pyruvate kinase M2 (PKM2)-mediated Warburg effect, namely aerobic glycolysis, in the regulation of high-mobility group box 1 (HMGB1) release. PKM2 interacts with hypoxia-inducible factor 1 alpha (HIF1 alpha) and activates the HIF-1 alpha-dependent transcription of enzymes necessary for aerobic glycolysis in macrophages. Knockdown of PKM2, HIF1 alpha and glycolysis-related genes uniformly decreases lactate production and HMGB1 release. Similarly, a potential PKM2 inhibitor, shikonin, reduces serum lactate and HMGB1 levels, and protects mice from lethal endotoxemia and sepsis. Collectively, these findings shed light on a novel mechanism for metabolic control of inflammation by regulating HMGB1 release and highlight the importance of targeting aerobic glycolysis in the treatment of sepsis and other inflammatory diseases. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://academicworks.medicine.hofstra.edu/publications/563Test; https://academicworks.medicine.hofstra.edu/context/publications/article/1564/viewcontent/NatCommun2014v5p4436.pdfTest |
| DOI: | 10.1038/ncomms5436 |
| الإتاحة: | https://doi.org/10.1038/ncomms5436Test https://academicworks.medicine.hofstra.edu/publications/563Test https://academicworks.medicine.hofstra.edu/context/publications/article/1564/viewcontent/NatCommun2014v5p4436.pdfTest |
| رقم الانضمام: | edsbas.14A2C512 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/ncomms5436 |
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