The Protein Level of Hypoxia-Inducible Factor-1α Is Increased in the Plateau Pika (Ochotona curzoniae) Inhabiting High Altitudes

The plateau pika (Ochotona curzoniae) is a high hypoxia-tolerant species living only at 3,000-5,000m 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-1 alpha protein in the pika by Western blot and immunohistochemical analysis. We found that HIF-1 alpha 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-1 alpha in the lung, liver, spleen and kidney of the pika were increased with increased habitat altitudes. We observed that the plateau pika HIF-1 alpha 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-1 alpha protein levels are related to the adaptation of the plateau pika to the high-altitude hypoxic environment. J. Exp. Zool. 311A:134-141, 2009. (c) 2008 Wiley-Liss, Inc.