title: The protein level of hypoxia-inducible factor-1alpha is increased in the plateau pika (Ochotona curzoniae) inhabiting high altitudes.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hong-Ge
authors.initials: HG
authors.lastname: Li
authors.forename: Yong-Ming
authors.initials: YM
authors.lastname: Ren
authors.forename: Song-Chang
authors.initials: SC
authors.lastname: Guo
authors.forename: Long
authors.initials: L
authors.lastname: Cheng
authors.forename: De-Peng
authors.initials: DP
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Chang
authors.forename: Xin-Quan
authors.initials: XQ
authors.lastname: Zhao
mesh_terms: D000220:Adaptation, Biological / Q000502:physiology*; D000531:Altitude; D000818:Animals; D015153:Blotting, Western; D002681:China; D017931:DNA Primers / Q000235:genetics; D017753:Ecosystem; D005455:Fluorescent Antibody Technique; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D007793:Lagomorpha / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008156:Luciferases; D008168:Lung / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism
chemical_list: D017931:DNA Primers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008156:Luciferases