Li Hong-Ge, Ren Yong-Ming, Guo Song-Chang, Cheng Long, Wang De-Peng, Yang Jie, Chang Zhi-Jie, Zhao Xin-Quan
Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, The Chinese Academy of Sciences, Xining, People's Republic of China.
J Exp Zool A Ecol Genet Physiol. 2009 Feb 1;311(2):134-41. doi: 10.1002/jez.510.
The plateau pika (Ochotona curzoniae) is a high hypoxia-tolerant species living only at 3,000-5,000 m above sea-level on the Qinghai-Tibetan plateau. Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates a variety of cellular and systemic adaptations to hypoxia. To investigate how the plateau pika adapts to a high-altitude hypoxic environment at the molecular level, we examined the expression pattern of the HIF-1alpha protein in the pika by Western blot and immunohistochemical analysis. We found that HIF-1alpha protein is expressed at a significantly high level in the pika, which is higher in most tissues (particularly in the lung, liver, spleen and kidney) of the plateau pika than that of mice living at sea-level. Importantly, we found that the protein levels of HIF-1alpha in the lung, liver, spleen and kidney of the pika were increased with increased habitat altitudes. We observed that the plateau pika HIF-1alpha localized to the nucleus of cells by an immunostaining analysis, and enhanced HRE-driven gene expression by luciferase reporter assays. Our study suggests that the HIF-1alpha protein levels are related to the adaptation of the plateau pika to the high-altitude hypoxic environment.
高原鼠兔（高原鼠兔）是一种高度耐缺氧的物种，仅生活在青藏高原海拔3000 - 5000米的地区。缺氧诱导因子-1（HIF-1）是一种关键的转录因子，可调节细胞和全身对缺氧的多种适应性反应。为了研究高原鼠兔在分子水平上如何适应高海拔缺氧环境，我们通过蛋白质免疫印迹和免疫组织化学分析检测了高原鼠兔中HIF-1α蛋白的表达模式。我们发现，高原鼠兔中HIF-1α蛋白的表达水平显著较高，在高原鼠兔的大多数组织（特别是肺、肝、脾和肾）中，其表达水平高于生活在海平面的小鼠。重要的是，我们发现随着栖息地海拔的升高，高原鼠兔肺、肝、脾和肾中HIF-1α的蛋白水平增加。我们通过免疫染色分析观察到高原鼠兔HIF-1α定位于细胞核，并通过荧光素酶报告基因检测增强了缺氧反应元件驱动基因的表达。我们的研究表明，HIF-1α蛋白水平与高原鼠兔对高海拔缺氧环境的适应性有关。
