Blunted nitric oxide regulation in Tibetans under high-altitude hypoxia

查看全文 作　　者：Yaoxi [1,2,3]He;Xuebin [1,3]Qi;[4]Ouzhuluobu;Shiming [5]Liu;Jun [6]Li;Hui [1,4]Zhang;[4]Baimakangzhuo;Caijuan [4]Bai;Wangshan [1]Zheng;Yongbo [1]Guo;[4]Duojizhuoma;[4]Baimayangji;[4]Dejiquzong;[4]Bianba;[4]Gonggalanzi;Yongyue [4]Pan;[4]Qula;[4]Kangmin;[4]Cirenyangji;Wei [4]Guo;[4]Yangla;Yi [1]Peng;Xiaoming [1]Zhang;Kun [1]Xiang;Zhaohui [7]Yang;Liangbang [5]Wang;[5]Gengdeng;Yanfeng [6]Zhang;Tianyi [5]Wu;Bing [1,3]Su;Chaoying [4]Cui

机构地区：[1]State Key Laboratory of Genetic Resources and Evolution,Kunming Instrtute of Zoology, Chinese Academy of Sciences,Kunmmg 650223,China;[2]Kunmmg College of Life Science,University of Chinese Academy of Sciences,Beijing100101,China;[3]Center for Excellence in Animal Evolution and Genetics.Chinese Academy of Sciences, Kunming 650223. China;[4]High Altitude Medical Research Center,School of Medicine.Tibetan University,Lhasa 850000,China;[5]National Key Laboratory of High Altitude Medicine, High Altitude Medical Research Institute, Xining 810012,China;[6]Fukang International Medical Examination Center,Fukang Obstetrics,Gynecology and Children Branch Hospital.Tibetan Fukang Hospital.Lhasa 850000,China;[7]Yunnan Key Laboratory of Primate Biomedicine Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology.Kunming 650500,China

出　　处：《National Science Review》索引2018年第5卷第4期,共14页

基　　金：supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13010000 to BS and XDA20040102 to XQ);the National Natural Science Foundation of China(91631306 to BS,31671329 and 31371269 to XQ,31460287 and 31660308 to Ouzhuluobu,31501013 to HZ and 31360032 to CC);the National 973 program(2012CB518202 to TW);the State Key Laboratory of Genetic Resources and Evolution(GREKF14-09);the West Light Doctoral Program(to XZ);the Zhufeng Scholar Program of Tibetan University 摘　　要：Nitric oxide(NO) is an important molecule for vasomotor tone, and elevated NO signaling was previously hypothesized as a unique and adaptive physiological change in highland Tibetans. However, there has been lack of NO data from Tibetans living at low altitude and lowlander immigrants living at high altitude, which is crucial to test this hypothesis. Here, through cross-altitude(1990–5018 m) and cross-population(Tibetans and Han Chinese) analyses of serum NO metabolites(NOx) of 2086 individuals, we demonstrate that although Tibetans have a higher serum NOx level compared to lowlanders, Han Chinese immigrants living at high altitude show an even higher level than Tibetans. Consequently, our data contradict the previous proposal of increased NO signaling as the unique adaptive strategy in Tibetans.Instead, Tibetans have a relatively lower circulating NOx level at high altitude. This observation is further supported by data from the hypoxic experiments using human umbilical vein endothelial cells and gene knockout mice. No difference is detected between Tibetans and Han Chinese for endothelial nitric oxide synthase(e NOS), the key enzyme for circulating NO synthesis, suggesting that e NOS itself is unlikely to be the cause. We show that other NO synthesis-related genes(e.g. GCH1) carry Tibetan-enriched mutations significantly associated with the level of circulating NOx in Tibetans. Furthermore, gene network analysis revealed that the downregulation and upregulation of NOx is possibly achieved through distinct pathways.Collectively, our findings provide novel insights into the physiological and genetic mechanisms of the evolutionary adaptation of Tibetans to high-altitude hypoxia. 关键词：ADAPTATION high ALTITUDE TIBETAN NITRIC OXIDE GCH1

相关文献

参考文献（52）
引证文献（8）
耦合文献（0）

参考文献(52)

引证文献(8)

互联网出版许可证新出网证(渝)字10号全国400电话 - 免长途话费

Blunted nitric oxide regulation in Tibetans under high-altitude hypoxia

参考文献(52)

引证文献(8)

用户提示