New insights on the regulation of the adenine nucleotide pool of erythrocytes in mouse models.
New insights on the regulation of the adenine nucleotide pool of erythrocytes in mouse models.
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DOI：
10.1371/journal.pone.0180948
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Lee CC
中科院分区：
文献类型：
--
作者：
O'Brien WG 3rd;Ling HS;Zhao Z;Lee CC
在非冬眠哺乳动物中诱导的昏睡可能是由于循环中AMP浓度增加导致的，这一观察结果使我们的研究揭示了添加的AMP改变了红细胞的氧转运。为了进一步研究AMP对红细胞功能和全身代谢的调节作用，我们建立了AMP代谢中关键红细胞酶缺陷的小鼠模型。我们以前曾报道过红细胞腺嘌呤核苷酸水平的改变对应于CD 73和AMPD 3缺陷小鼠氧饱和度的改变。在这里，我们进一步研究了这些Ampd 3-/-/Cd 73-/-小鼠如何与单酶缺乏症和野生型对照模型相比对AMP给药剂量的反应。我们发现Ampd 3-/-/Cd 73-/-小鼠对AMP诱导的低代谢比单一酶缺乏的小鼠更敏感，后者比野生型更敏感。红细胞p50值随细胞外AMP浓度的增加而发生剂量依赖性的显著变化。我们提供了进一步的证据表明，AMP的直接摄取红细胞是不敏感的双嘧达莫，一个阻滞剂ENT 1。红细胞对AMP的摄取在测试的最高浓度10 mM下保持线性。我们还观察到竞争性抑制AMP摄取ATP和ADP，但不是由其他核苷酸和代谢物测试。重要的是，我们的研究表明，AMP摄取与红细胞ATP释放有关，红细胞ATP释放对TRO 19622和Ca++离子的抑制部分敏感。综上所述，我们的研究提出了一种新的机制，红细胞通过AMP摄取和ATP释放来回收和维持其腺嘌呤核苷酸库。
The observation that induced torpor in non-hibernating mammals could result from an increased AMP concentration in circulation led our investigation to reveal that the added AMP altered oxygen transport of erythrocytes. To further study the effect of AMP in regulation of erythrocyte function and systemic metabolism, we generated mouse models deficient in key erythrocyte enzymes in AMP metabolism. We have previously reported altered erythrocyte adenine nucleotide levels corresponding to altered oxygen saturation in mice deficient in both CD73 and AMPD3. Here we further investigate how these Ampd3-/-/Cd73-/- mice respond to the administered dose of AMP in comparison with the control models of single enzyme deficiency and wild type. We found that Ampd3-/-/Cd73-/- mice are more sensitive to AMP-induced hypometabolism than mice with a single enzyme deficiency, which are more sensitive than wild type. A dose-dependent rightward shift of erythrocyte p50 values in response to increasing amounts of extracellular AMP was observed. We provide further evidence for the direct uptake of AMP by erythrocytes that is insensitive to dipyridamole, a blocker for ENT1. The uptake of AMP by the erythrocytes remained linear at the highest concentration tested, 10mM. We also observed competitive inhibition of AMP uptake by ATP and ADP but not by the other nucleotides and metabolites tested. Importantly, our studies suggest that AMP uptake is associated with an erythrocyte ATP release that is partially sensitive to inhibition by TRO19622 and Ca++ ion. Taken together, our study suggests a novel mechanism by which erythrocytes recycle and maintain their adenine nucleotide pool through AMP uptake and ATP release.
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影响因子：
3.7
作者：
Daniels IS;O Brien WG 3rd;Nath V;Zhao Z;Lee CC
通讯作者：
Lee CC
影响因子：
4
作者：
Goldman D;Fraser GM;Ellis CG;Sprague RS;Ellsworth ML;Stephenson AH
通讯作者：
Stephenson AH
DOI：
10.1152/ajpheart.00998.2011
发表时间：
2012-02-01
影响因子：
4.8
作者：
Sridharan, Meera;Bowles, Elizabeth A.;Sprague, Randy S.
通讯作者：
Sprague, Randy S.
DOI：
10.1016/j.jchromb.2012.02.005
发表时间：
2012-03-15
影响因子：
3
作者：
Bhatt, Dhaval P.;Chen, Xuesong;Geiger, Jonathan D.;Rosenberger, Thad A.
通讯作者：
Rosenberger, Thad A.
影响因子：
4.8
作者：
Fiermonte, Giuseppe;Paradies, Eleonora;Palmieri, Ferdinando
通讯作者：
Palmieri, Ferdinando