Variations of Corticotropin-Releasing Factor Receptor 1α Contribute to the Blunted HPA Axis Responses to Hypoxia in Plateau Mammals
文献类型：期刊论文
| 作者 | Yang, Jiafang; Xia, Fangyuan; Jin, Hao; Mahanand, Chatoo; Lin, Huiqi; Cao, Yibin; Bian, Jianghui; Wei, Dengbang; Nevo, Eviatar; Du, Jizeng |
| 刊名 | NEUROSCIENCE BULLETIN
 |
| 出版日期 | 2025 |
| 关键词 | CRF CRFR1 alpha HPA cAMP Extreme environment Stress |
| 英文摘要 | Corticotropin-releasing factor (CRF) and its receptor (CRFR1) are critical components of the hypothalamic-pituitary-adrenocortical (HPA) axis. Ochotona curzoniae (O. curzoniae), Myospalax baileyi (M. baileyi), and Microtus oeconomus (M. oeconomus) have diversely evolved adaptive strategies to the extreme environment at high altitude. Here, we found blunted HPA axis responsiveness in native Tibetan mammals. CRF was 100% conserved, three amino-acid variations were in M. oeconomus-urocortin (UCN), and unique amino-acid variations in ligand-receptor binding domains of O. curzoniae-, M. baileyi-, and M. oeconomus-CRFR1 alpha s. The native mammals' binding affinity and cAMP production varied depending on different doses of ligand-CRF/UCN treatment. Variations in M. oeconomus-UCN and O. curzoniae-, M. baileyi-, M. oeconomus-CRFR1 alpha were responsible for weaker CRF-CRFR1 alpha binding and higher EC50. They had the same HPA response pattern as that of CRF-CRFR1 alpha binding affinity, cAMP production, and cell permeability. AlphaFold3.0 predicted altered structural interactions for both CRF-CRFR1 alpha and UCN-CRFR1 alpha complexes corroborate our findings. This study reveals that the variations of UCN/CRFR1 alpha contribute to the different responsiveness of the HPA axis to extreme environments. |
| 源URL | [http://210.75.249.4/handle/363003/62318]  |
| 专题 | 西北高原生物研究所_中国科学院西北高原生物研究所 |
| 推荐引用方式 GB/T 7714 | Yang, Jiafang,Xia, Fangyuan,Jin, Hao,et al. Variations of Corticotropin-Releasing Factor Receptor 1α Contribute to the Blunted HPA Axis Responses to Hypoxia in Plateau Mammals[J]. NEUROSCIENCE BULLETIN,2025. |
| APA | Yang, Jiafang.,Xia, Fangyuan.,Jin, Hao.,Mahanand, Chatoo.,Lin, Huiqi.,...&Chen, Xuequn.(2025).Variations of Corticotropin-Releasing Factor Receptor 1α Contribute to the Blunted HPA Axis Responses to Hypoxia in Plateau Mammals.NEUROSCIENCE BULLETIN. |
| MLA | Yang, Jiafang,et al."Variations of Corticotropin-Releasing Factor Receptor 1α Contribute to the Blunted HPA Axis Responses to Hypoxia in Plateau Mammals".NEUROSCIENCE BULLETIN (2025). |
入库方式： OAI收割
来源：西北高原生物研究所
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