A Role of Erythrocytes in Adenosine Monophosphate Initiation of Hypometabolism in Mammals
A Role of Erythrocytes in Adenosine Monophosphate Initiation of Hypometabolism in Mammals
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DOI：
10.1074/jbc.m109.090845
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发表时间：
2010-07-02
影响因子：
4.8
通讯作者：
Lee, Cheng Chi
中科院分区：
文献类型：
--
作者：
Daniels, Isadora Susan;Zhang, Jianfa;Lee, Cheng Chi
对哺乳动物中各种低代谢状态如何启动的生物化学和机制方面了解甚少。在这里，我们展示了红细胞对5 '-AMP的摄取是如何引发代谢减退的。野生型、外-5 '-核苷酸酶缺陷型和腺苷受体缺陷型小鼠以类似的方式经历5'-AMP诱导的低代谢。注射5 '-AMP导致氧消耗（VO 2）的两个不同的下降阶段。I相反应显示VO 2快速急剧下降，与体温（T-b）和环境温度（T-a）无关。随后是与T-b相关并由T-a调节的第二阶段下降。将5 '-AMP的剂量从0.25倍改变到2倍不会改变I相反应。对于小鼠，15 ℃的T-a对于用适当剂量的5 ′-AMP诱导DH是有效的。红细胞摄取5 '-AMP导致利用ATP合成ADP。这伴随着葡萄糖增加，但乳酸水平降低，表明糖酵解已经减缓。已知糖酵解的减少会刺激红细胞增加细胞内2，3-二磷酸甘油酸的水平，2，3-二磷酸甘油酸是血红蛋白对氧亲和力的有效变构抑制剂。我们的研究表明，2，3-二磷酸甘油酸和脱氧血红蛋白水平在5 '-AMP给药后升高，并与VO 2的I期下降平行。总之，我们的研究表明，5 '-AMP介导的代谢减退可能是由红细胞摄取5'-AMP引起的氧转运减少引发的。
Biochemical and mechanistic aspects into how various hypometabolic states are initiated in mammals are poorly understood. Here, we show how a state of hypometabolism is initiated by 5'-AMP uptake by erythrocytes. Wild type, ecto-5'-nucleotidase-deficient, and adenosine receptor-deficient mice undergo 5'-AMP-induced hypometabolism in a similar fashion. Injection of 5'-AMP leads to two distinct declining phases of oxygen consumption (VO2). The phase I response displays a rapid and steep decline in VO2 that is independent of body temperature (T-b) and ambient temperature (T-a). It is followed by a phase II decline that is linked to T-b and moderated by T-a. Altering the dosages of 5'-AMP from 0.25- to 2-fold does not change the phase I response. For mice, a T-a of 15 degrees C is effective for induction of DH with the appropriate dose of 5'-AMP. Erythrocyte uptake of 5'-AMP leads to utilization of ATP to synthesize ADP. This is accompanied by increased glucose but decreased lactate levels, suggesting that glycolysis has slowed. Reduction in glycolysis is known to stimulate erythrocytes to increase intracellular levels of 2,3-bisphosphoglycerate, a potent allosteric inhibitor of hemoglobin's affinity for oxygen. Our studies showed that both 2,3-bisphosphoglycerate and deoxyhemoglobin levels rose following 5'-AMP administration and is in parallel with the phase I decline in VO2. In summary, our investigations reveal that 5'-AMP mediated hypometabolism is probably triggered by reduced oxygen transport by erythrocytes initiated by uptake of 5'-AMP.