Increased hypoxic stress decreases AMP hydrolysis in rabbit heart.
Increased hypoxic stress decreases AMP hydrolysis in rabbit heart.
复制标题
缺氧应激增加会降低兔心脏中的 AMP 水解。
DOI：
10.1016/s0008-6363(99)00207-2
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发表时间：
1999
影响因子：
10.8
通讯作者：
Kroll,K
中科院分区：
文献类型：
--
作者：
Gustafson,LA;Zuurbier,CJ;Bassett,JE;Barends,JP;vanBeek,JH;Bassingthwaighte,JB;Kroll,K
目的：在复氧过程中，胞浆5‘-核苷酸酶(5NT)将AMP转化为腺苷，或AMP脱氨酶将AMP转化为IMP，这决定了核苷酸降解的程度，从而决定了ATP的再合成。为了阐明AMP在缺血过程中的水解规律，通过数学模型将31P核磁共振波谱和生化分析的数据结合在一起。由于5NT在严重低灌流(5%流量)时被下调，我们测试了在轻度低灌流(10%流量)时5NT的调节，然后使灌流液低氧，看看更大的压力是否重新激活了5NT。方法：在两个30min的低灌注期(10%流量)，第二阶段有或没有额外的低氧(30%O2)，获得31P核磁共振波谱和冠状静脉流出物。结果：10%流量的单次30min可引起AMP水解酶的下调，而第二次低灌注期的数据最好用更低的5NT活性来描述，即使在额外缺氧的情况下也是如此。当模型不允许IMP积累时，静脉流出液中的嘌呤比光能学(PCR和ATP)预测的少30%，但该模型表明，通过AMP脱氨酶持续积累的IMP可以解释静脉流出液中预期的和实际的嘌呤之间的差异。结论：虽然AMP在早期缺血时显著地水解为腺苷，并起到保护细胞能量潜力的作用，但在第二个缺血期，核苷酸通过稳定的AMP水解酶的抑制而保守。此外，在10%的流动条件下，核苷酸是保守的，可能是通过IMP积累途径。
Objective:AMP conversion to adenosine by cytosolic 5′-nucleotidase (5NT) or to IMP by AMP deaminase determines the degree of nucleotide degradation, and thus ATP resynthesis, during reoxygenation. To elucidate the regulation of AMP hydrolysis during ischemia, data from31P NMR spectroscopy and biochemical analyses were integrated via a mathematical model. Since 5NT is downregulated during severe underperfusion (5% flow), we tested 5NT regulation during less severe underperfusion (10% flow) and then made the perfusate hypoxic to see if the greater stress reactivated 5NT.Methods:31P NMR spectra and coronary venous effluents were obtained from Langendorff-perfused rabbit hearts subjected to two 30-min periods of underperfusion (10% flow); the second period with or without additional hypoxia (30% O2). Data were analyzed with a mathematical model describing the kinetics of myocardial energetics and metabolism.Results:A single 30-min period of 10% flow causes downregulation of AMP hydrolysis and the data from the second period of underperfusion are best described by lower 5NT activity, even in the presence of extra hypoxia. Thirty percent less purines appear in the venous effluent than predicted by the phosphoenergetics (PCr and ATP) when IMP is not allowed to accumulate by the model, however the model indicates that a constant accumulation of IMP via AMP deaminase could explain the discrepancy between expected and measured purines in the venous effluent.Conclusions:While AMP hydrolysis to adenosine is prominent in early ischemia and acts to preserve cellular energy potential, during a second ischemic period, nucleotides are conserved by the stable inhibition of AMP hydrolysis. Furthermore, during 10% flow conditions, nucleotides are conserved, possibly via an IMP-accumulatory pathway.