4.8 Article

A homotetrameric hemoglobin expressed in alveolar epithelial cells increases blood oxygenation in high-altitude plateau pika (Ochotona curzoniae)

期刊

CELL REPORTS
卷 41, 期 1, 页码 -

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CELL PRESS
DOI: 10.1016/j.celrep.2022.111446

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资金

  1. National Natural Science Foundation of China [31860606]
  2. Second Tibetan Plateau Scientific Expedition and Research Program (STEP) [2019 QZKK0501]
  3. Natural Science Foundation of Qinghai Province of China [2020-ZJ-959Q]
  4. Chinese Academy of Sciences-People's Government of Qinghai Province on Sanjiangyuan National Park [LHZX-2020-01]

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This study investigates the expression of the protein HBD in the lungs of plateau pikas and finds that when HBD expression is downregulated, the pikas show hypoxemia. These findings provide insights into the adaptive mechanisms of plateau pikas in high-altitude environments.
The plateau pika (Ochotona curzoniae) is native to the Qinghai-Tibet Plateau. In this study, the gene that en-codes a heme-binding protein in the pulmonary surfactant (PS) of the pika is identified. The protein is a ho-motetrameric hemoglobin (84) encoded by HBD (d). HBD is expressed in alveolar epithelial type II (ATII) and type I (ATI) cells, upregulated by hypoxia. 84 is secreted into alveolar cavities through osmiophilic multilamel-lar bodies. HBD expression is downregulated by RNAi, which significantly increases hypoxia-inducible factor 1a expression in lung tissue and red blood cells and hemoglobin and blood lactate concentrations but signif-icantly decreases arterial partial pressure of oxygen (PaO2). Our results indicate that plateau pikas physiolog-ically show hypoxemia when HBD expression is downregulated. Therefore, specific HBD expression in the lungs helps plateau pikas to obtain oxygen under hypoxia by maintaining higher PaO2. These findings provide insights into the adaptive mechanisms of plateau pikas to withstand high-altitude environments.

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