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Natural product P57 induces hypothermia through targeting pyridoxal kinase

文献类型：期刊论文

作者Wang, Ruina4; Xiao, Lei5; Pan, Jianbo6; Bao, Guangsen4; Zhu, Yunmei6; Zhu, Di4; Wang, Jun1; Pei, Chengfeng10; Ma, Qinfeng6; Fu, Xian6
刊名NATURE COMMUNICATIONS
出版日期2023-09-26
卷号14期号:1页码:15
DOI10.1038/s41467-023-41435-y
通讯作者Jiang, Wei(jiangw@fudan.edu.cn) ; Luo, Cheng(cluo@simm.ac.cn) ; Yu, Biao(byu@mail.sioc.ac.cn) ; Dang, Yongjun(yjdang@cqmu.edu.cn)
英文摘要Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme environmental conditions. However, pharmacological induction of hypothermia in most mammals remains a huge challenge. Here we show that a natural product P57 promptly induces hypothermia and decreases energy expenditure in mice. 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 blunted in the mice with knockout of PDXK in the preoptic area (POA) of hypothalamus. We further found that P57 and PL have consistent effects on gene expression regulation in hypothalamus, and they may activate medial preoptic area (MPA) neurons in POA 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 hypothermia state in mice.
WOS关键词PHARMACOLOGICALLY INDUCED HYPOTHERMIA ; THERAPEUTIC HYPOTHERMIA ; BODY-TEMPERATURE ; HOODIA-GORDONII ; ISCHEMIC NEUROPROTECTION ; APPETITE-SUPPRESSANT ; PREOPTIC NEURONS ; HYPOTHALAMUS ; STROKE ; MODEL
资助项目National Natural Science Foundation of China[22137002] ; National Natural Science Foundation of China[21877016] ; National Natural Science Foundation of China[22031011] ; National Natural Science Foundation of China[21621002] ; National Natural Science Foundation of China[91853205] ; National Natural Science Foundation of China[81625022] ; National Natural Science Foundation of China[81972621] ; National Natural Science Foundation of China[92253305] ; National Natural Science Foundation of China[81970727] ; National Natural Science Foundation of China[31900738] ; Science and Technology Commission of Shanghai Municipality[20JC1410900] ; University Innovation Research Group in Chongqing[CXQT21016] ; Chongqing Talent Program Project[CQYC20200302119] ; High-Level Innovation Platform Cultivation Plan of Chongqing ; Natural Science Innovation and Development Foundation of Chongqing ; Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning ; Fund of the State Key Laboratory of Bioorganic and Natural Products Chemistry[SKLBNPC16233] ; Key Research Program of Frontier Sciences of the Chinese Academy of Sciences[ZDBS-LY-SLH030] ; Shanghai Municipal Science and Technology Major Project[2018SHZDZX01] ; Shanghai Pujiang Program[19PJ1401800] ; Shanghai Center for Brain Science and Brain-Inspired Technology
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PORTFOLIO
WOS记录号WOS:001128353900007
源URL[http://119.78.100.183/handle/2S10ELR8/308535]  
专题新药研究国家重点实验室
通讯作者Jiang, Wei; Luo, Cheng; Yu, Biao; Dang, Yongjun
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
2.Univ Calif San Francisco, Cardiovasc Res Inst, Dept Physiol, San Francisco, CA USA
3.Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Shanghai, Peoples R China
4.Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, Dept Biochem & Mol Biol,Minist Educ,Key Lab Metab, Shanghai, Peoples R China
5.Fudan Univ, Shanghai Med Coll, Inst Brain Sci, State Key Lab Med Neurobiol, Shanghai, Peoples R China
6.Chongqing Med Univ, Affiliated Hosp 2, Inst Life Sci, Minist Educ,Basic Med Res & Innovat Ctr Novel T, Chongqing, Peoples R China
7.China Pharmaceut Univ, Dept Med Chem, Nanjing, Peoples R China
8.Fudan Univ, Basic Med Sch, Dept Human Anat Histol & Embryol, Lab Tumor Immunol, Shanghai, Peoples R China
9.Naval Med Univ, Dept Pharmacol, Coll Pharm, Shanghai, Peoples R China
10.Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Bioorgan & Nat Prod Chem, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Ruina,Xiao, Lei,Pan, Jianbo,et al. Natural product P57 induces hypothermia through targeting pyridoxal kinase[J]. NATURE COMMUNICATIONS,2023,14(1):15.
APA Wang, Ruina.,Xiao, Lei.,Pan, Jianbo.,Bao, Guangsen.,Zhu, Yunmei.,...&Dang, Yongjun.(2023).Natural product P57 induces hypothermia through targeting pyridoxal kinase.NATURE COMMUNICATIONS,14(1),15.
MLA Wang, Ruina,et al."Natural product P57 induces hypothermia through targeting pyridoxal kinase".NATURE COMMUNICATIONS 14.1(2023):15.

入库方式： OAI收割

来源：上海药物研究所

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