A homotetrameric hemoglobin expressed in alveolar epithelial cells increases blood oxygenation in high-altitude plateau pika (Ochotona curzoniae)
Zhifang An,
Linna Wei,
Bo Xu,
Zhijie Wang,
Conghui Gao,
Jimei Li,
Lian Wei,
Delin Qi,
Peng Shi,
Tongzuo Zhang,
Dengbang Wei
Affiliations
Zhifang An
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University 10743, Xining, Qinghai 810016, China
Linna Wei
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University 10743, Xining, Qinghai 810016, China
Bo Xu
Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai 810008, China
Zhijie Wang
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University 10743, Xining, Qinghai 810016, China
Conghui Gao
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University 10743, Xining, Qinghai 810016, China
Jimei Li
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University 10743, Xining, Qinghai 810016, China
Lian Wei
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University 10743, Xining, Qinghai 810016, China
Delin Qi
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University 10743, Xining, Qinghai 810016, China
Peng Shi
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Corresponding author
Tongzuo Zhang
Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai 810008, China; Corresponding author
Dengbang Wei
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University 10743, Xining, Qinghai 810016, China; Corresponding author
Summary: The plateau pika (Ochotona curzoniae) is native to the Qinghai-Tibet Plateau. In this study, the gene that encodes a heme-binding protein in the pulmonary surfactant (PS) of the pika is identified. The protein is a homotetrameric hemoglobin (δ4) encoded by HBD (δ). HBD is expressed in alveolar epithelial type II (ATII) and type I (ATI) cells, upregulated by hypoxia. δ4 is secreted into alveolar cavities through osmiophilic multilamellar bodies. HBD expression is downregulated by RNAi, which significantly increases hypoxia-inducible factor 1α expression in lung tissue and red blood cells and hemoglobin and blood lactate concentrations but significantly decreases arterial partial pressure of oxygen (PaO2). Our results indicate that plateau pikas physiologically 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.
