| Autor: |
Yongjun Dang, Rui-Na Wang, Lei Xiao, Jianpo Pan, Di Zhu, Jun Wang, Chengfeng Pei, Qinfeng Ma, Guangsen Bao, Ziruoyu Wang, Mengdi Zhu, Guoxiang Wang, Ling Gong, Qiuping Tong, Min Jiang, Junchi Hu, Miao He, Yun Wang, Tiejun li, Wei Li, Chun-Min Liang, Zengxia Li, Dengke Ma, Minjia Tan, Jun-Yan Liu, Wei Jiang, Cheng Luo, Biao Yu |
| Rok vydání: |
2022 |
| Popis: |
Hibernation/torpor enables certain mammals to survive under extreme environmental conditions. However, pharmacological induction of hibernation-like or torpor state in most mammals remains a huge challenge. Here we show that a natural product P57 promptly induces hypothermia and decreases energy expenditure in rodents. Mechanistically, P57 inhibits the kinase activity of pyridoxal kinase (PDXK), a key metabolic enzyme of vitamin B6 catalyzing phosphorylation of pyridoxal (PL), resulting in the accumulation of PL in hypothalamus to cause hypothermia. The hypothermia induced by P57 is significantly recuperated in the mice with knockout of PDXK in medial preoptic area (MPA). We further found that P57 and PL have consistent effects on gene expression regulation in hypothalamus, and both directly activate MPA neurons to induce hypothermia. Taken together, our findings demonstrate that P57 has a potential application in therapeutic hypothermia through regulation of vitamin B6 metabolism and PDXK serves as a previously unknown target of P57 in thermoregulation. In addition, P57 may serve as a chemical probe for exploring the neuron circuitry related to hibernation-like state in rodents. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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