Submitted on June 7, 2006
Accepted on September 12, 2006
Diversities in hepatic HIF-1, IGF-I/IGFBP-1, LDH/ICD, and their mRNA expressions induced by CoCl2 in Qinghai-Tibetan Plateau mammals and sea level mice
Xue Qun Chen1, Shi Jun Wang1, Ji Zeng Du1*, and Xiao Chen Chen2
1 Neurobiology and Physiology, Zhejiang University, Hangzhou, Zhejiang, China
2 Northwest Plateau Institute of Biology, The Chinese Academy of Sciences, Xining, Qinghai, China
* To whom correspondence should be addressed. E-mail: dujz{at}cls.zju.edu.cn.
Ochotona curzoniae and Microtus oeconomus are the native mammals living on the Qinghai-Tibetan-Plateau of China. The molecular mechanisms of their acclimatization to the Plateau-hypoxia remain unclear. Expressions of Hepatic HIF-1
, IGF-I/IGFBP-1(including genes), and key metabolic enzymatic genes (LDH-A/ICD) are compared in Qinghai-Tibetan-Plateau' mammals and sea-level mice after injection of CoCl2 (20, 40, or 60mg/kg) and normobaric hypoxia (16.0%O2, 10.8%O2, and 8.0%O2) for 6h, tested by histochemistry, Western blot, ELISA, and RT-PCR. Major results are: CoCl2 markedly increased (a) HIF-1 only in mice, (b) hepatic and circulatory IGF-I in M. oeconomus, (c) hepatic IGFBP-1 in mice and O. curzoniae, and (d) LDH-A but reduced ICDmRNA in mice (CoCl2 20mg/kg), but unchanged in the Tibetan mammals. Normobaric hypoxia markedly (a) increased HIF-1 and LDH-A mRNA in mice and M. oeconomus (8.0%O2) not in O. curzoniae and (b) reduced ICDmRNA in mice and M. oeconomus (8.0%O2) not in O. curzoniae. Results suggest that (1) HIF-1 responsiveness to hypoxia is distinct in lowland mice and Plateau mammals, reflecting a diverse tolerance of the three species to hypoxia; (2) CoCl2 induce diversities in HIF-1, IGF-I/ IGFBP-1 protein or genes in mice, M. oeconomus, and O. curzoniae. In contrast, HIF-1 mediates IGFBP-1 transcription only in mice and in M. oeconomus (subjected to severe hypoxia), (3) Differences in IGF-I/IGFBP-1 expressions induced by CoCl2 reflect a significant diversities in hormone regulation and cell protection from damage. (4) Activation of anaerobic glycolysis and reduction of Krebs cycle represents strategies of lowland-animals vs. the stable metabolic homeostasis of plateau-acclimatized mammals.
