Li Jimei, An Zhifang, Wei Linna, Xu Bo, Wang Zhijie, Gao Conghui, Wei Lian, Qi Delin, Shi Peng, Zhang Tongzuo, Wei Dengbang
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, China.
Research Center for High Altitude Medicine, Qinghai University, Xining, China.
Front Genet. 2022 Mar 15;13:824049. doi: 10.3389/fgene.2022.824049. eCollection 2022.
The plateau zokor () is a native species to the Qinghai-Tibetan Plateau, inhabiting hypoxia and hypercapnia sealed subterranean burrows that pose several unique physiological challenges. In this study, we observed a novel heme-containing protein in the pulmonary surfactant (PS) of plateau zokor, identified the encoding gene of the protein, predicted its origination and structure, verified its expression in alveolar epithelial cells, and determined the protein's affinity to oxygen and its effect on the oxygen-dissolving capability in the PS of plateau zokors. The protein is an unusual homotetramer hemoglobin consisting of four subunits, and the subunit is encoded by a paralog gene of that is . The divergence time of from is estimated by the molecular clock to be about 2.45 Mya. The generation of in plateau zokors might well relate to long-time stress of the high land hypoxia. Unlike the has a hypoxia response element (HRE) and a lung tissue-specific enhancer in its upstream region, and it is expressed specifically in lung tissues and up-regulated by hypoxia. The protein is named as γ-like which is expressed specifically in Alveolar epithelial type II (ATII) cells and secreted into the alveolar cavities through the osmiophilic multilamellar body (LBs). The γ-like has a higher affinity to oxygen, and that increases significantly oxygen-dissolving capability in the PS of plateau zokors by its oxygenation function, which might be beneficial for the plateau zokors to obtain oxygen from the severe hypoxia environments by facilitating oxygen diffusion from alveoli to blood.
高原鼢鼠（）是青藏高原的本土物种，栖息于缺氧和高碳酸血症的封闭地下洞穴中，这带来了一些独特的生理挑战。在本研究中，我们在高原鼢鼠的肺表面活性物质（PS）中观察到一种新型含血红素蛋白，鉴定了该蛋白的编码基因，预测了其起源和结构，验证了其在肺泡上皮细胞中的表达，并确定了该蛋白对氧气的亲和力及其对高原鼢鼠PS中氧气溶解能力的影响。该蛋白是一种由四个亚基组成的不寻常的同型四聚体血红蛋白，亚基由的一个旁系同源基因编码，该基因长度为。通过分子钟估计与的分歧时间约为245万年前。高原鼢鼠中该基因的产生很可能与高原长期缺氧应激有关。与不同，该基因在其上游区域有一个缺氧反应元件（HRE）和一个肺组织特异性增强子，它在肺组织中特异性表达并受缺氧上调。该蛋白被命名为γ样蛋白，它在肺泡II型上皮（ATII）细胞中特异性表达，并通过嗜锇多层小体（LBs）分泌到肺泡腔中。γ样蛋白对氧气具有更高的亲和力，并且通过其氧合功能显著提高了高原鼢鼠PS中的氧气溶解能力，这可能有利于高原鼢鼠通过促进氧气从肺泡向血液的扩散，从严重缺氧环境中获取氧气。
