AMP deaminase 3 deficiency enhanced 5'-AMP induction of hypometabolism.
AMP deaminase 3 deficiency enhanced 5'-AMP induction of hypometabolism.
复制标题
DOI：
10.1371/journal.pone.0075418
复制
发表时间：
2013
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：
Daniels IS;O Brien WG 3rd;Nath V;Zhao Z;Lee CC
给予 5'-AMP 可以在小鼠中诱导低代谢状态。之前我们提出，这种代谢低下的潜在机制与由于 5'-AMP 摄取改变细胞腺苷酸平衡而导致红细胞氧运输功能降低有关。为了验证这一假设，我们培育了缺乏腺苷单磷酸脱氨酶 3 (AMPD3) 的小鼠，AMPD3 是红细胞中 5'-AMP 的关键分解代谢酶。缺乏 AMPD3 的小鼠在除红细胞外的所有组织中均保持 AMPD 活性。从发育和形态上看，Ampd3−/− 小鼠与其野生型小鼠没有什么区别。 Ampd3−/− 小鼠红细胞中 ATP、ADP 水平显着升高，但 5'-AMP 水平不显着升高。 Ampd3−/− 小鼠的空腹血糖水平与野生型小鼠相当。与野生型小鼠相比，Ampd3−/− 小鼠表现出更严重的代谢减退，响应 5'-AMP 给药的平均唤醒时间显着延迟。总之，这些发现证明了 AMPD3 在调节 5'-AMP 介导的代谢低下中发挥着核心作用，并进一步表明红细胞参与了这种行为反应。
A hypometabolic state can be induced in mice by 5′-AMP administration. Previously we proposed that an underlying mechanism for this hypometabolism is linked to reduced erythrocyte oxygen transport function due to 5′-AMP uptake altering the cellular adenylate equilibrium. To test this hypothesis, we generated mice deficient in adenosine monophosphate deaminase 3 (AMPD3), the key catabolic enzyme for 5′-AMP in erythrocytes. Mice deficient in AMPD3 maintained AMPD activities in all tissues except erythrocytes. Developmentally and morphologically, the Ampd3−/− mice were indistinguishable from their wild type siblings. The levels of ATP, ADP but not 5′-AMP in erythrocytes of Ampd3−/− mice were significantly elevated. Fasting blood glucose levels of the Ampd3−/− mice were comparable to wild type siblings. In comparison to wild type mice, the Ampd3−/− mice displayed a deeper hypometabolism with a significantly delayed average arousal time in response to 5′-AMP administration. Together, these findings demonstrate a central role of AMPD3 in the regulation of 5′-AMP mediated hypometabolism and further implicate erythrocytes in this behavioral response.
登录
查看更多内容
影响因子：
64.8
作者：
Skarnes WC;Rosen B;West AP;Koutsourakis M;Bushell W;Iyer V;Mujica AO;Thomas M;Harrow J;Cox T;Jackson D;Severin J;Biggs P;Fu J;Nefedov M;de Jong PJ;Stewart AF;Bradley A
通讯作者：
Bradley A
影响因子：
15.9
作者：
Castrop, H;Huang, YN;Schnermann, J
通讯作者：
Schnermann, J
影响因子：
2.2
作者：
IKEDA, S
通讯作者：
IKEDA, S
影响因子：
3.1
作者：
Mathews, WB;Nakamoto, Y;Wahl, RL
通讯作者：
Wahl, RL
DOI：
10.1152/ajpregu.00888.2006
发表时间：
2007-07-01
影响因子：
2.8
作者：
Swoap, Steven J.;Rathvon, Meaghan;Gutilla, Margaret
通讯作者：
Gutilla, Margaret