Effects of hypobaric hypoxia on adenine nucleotide pools, adenine nucleotide transporter activity and protein expression in rat liver. 2006

Cong-Yang Li, and Jun-Ze Liu, and Li-Ping Wu, and Bing Li, and Li-Fen Chen
Department of Pathophysiology, Institute of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, China.

OBJECTIVE To explore the effect of hypobaric hypoxia on mitochondrial energy metabolism in rat liver. METHODS Adult male Wistar rats were exposed to a hypobaric chamber simulating 5,000 m high altitude for 23 h every day for 0 (H0), 1 (H1), 5 (H5), 15 (H15) and 30 d (H30) respectively. Rats were sacrificed by decapitation and liver was removed. Liver mitochondria were isolated by differential centrifugation program. The size of adenine nucleotide pool (ATP, ADP, and AMP) in tissue and mitochondria was separated and measured by high performance liquid chromatography (HPLC). The adenine nucleotide transporter (ANT) activity was determined by isotopic technique. The ANT total protein level was determined by Western blot. RESULTS Compared with H0 group, intra-mitochondrial ATP content decreased in all hypoxia groups. However, the H5 group reached the lowest point (70.6%) (P<0.01) when compared to the control group. Intra-mitochondrial ADP and AMP level showed similar change in all hypoxia groups and were significantly lower than that in H0 group. In addition, extra-mitochondrial ATP and ADP content decreased significantly in all hypoxia groups. Furthermore, extra-mitochondrial AMP in groups H5, H15 and H30 was significantly lower than that in H0 group, whereas H1 group had no marked change compared to the control situation. The activity of ANT in hypoxia groups decreased significantly, which was the lowest in H5 group (55.7%) (P<0.01) when compared to H0 group. ANT activity in H30 group was higher than in H15 group, but still lower than that in H0 group. ANT protein level in H5, H15, H30 groups, compared with H0 group decreased significantly, which in H5 group was the lowest, being 27.1% of that in H0 group (P<0.01). ANT protein level in H30 group was higher than in H15 group, but still lower than in H0 group. CONCLUSIONS Hypobaric hypoxia decreases the mitochondrial ATP content in rat liver, while mitochondrial ATP level recovers during long-term hypoxia exposure. The lower level of extra-mitochondrial ATP may be related to the decrease of ANT activity during hypoxia exposure.

UI MeSH Term Description Entries
D008297 Male Males
D008930 Mitochondria, Liver Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4) Liver Mitochondria,Liver Mitochondrion,Mitochondrion, Liver
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
D000226 Mitochondrial ADP, ATP Translocases A class of nucleotide translocases found abundantly in mitochondria that function as integral components of the inner mitochondrial membrane. They facilitate the exchange of ADP and ATP between the cytosol and the mitochondria, thereby linking the subcellular compartments of ATP production to those of ATP utilization. ADP,ATP Carrier,ADP,ATP Translocator Protein,Adenine Nucleotide Translocase,ADP Translocase,ATP Translocase,ATP,ADP-Carrier,ATP-ADP Translocase,Adenine Nucleotide Carrier (Mitochondrial),Mitochondrial ADP-ATP Carriers,ADP-ATP Carriers, Mitochondrial,Mitochondrial ADP ATP Carriers
D000227 Adenine Nucleotides Adenine Nucleotide,Adenosine Phosphate,Adenosine Phosphates,Nucleotide, Adenine,Nucleotides, Adenine,Phosphate, Adenosine,Phosphates, Adenosine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000860 Hypoxia Sub-optimal OXYGEN levels in the ambient air of living organisms. Anoxia,Oxygen Deficiency,Anoxemia,Deficiency, Oxygen,Hypoxemia,Deficiencies, Oxygen,Oxygen Deficiencies
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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