Cellular metabolism of water-soluble nitroxides: effect on rate of reduction of cell/nitroxide ratio, oxygen concentrations and permeability of nitroxides.
Cellular metabolism of water-soluble nitroxides: effect on rate of reduction of cell/nitroxide ratio, oxygen concentrations and permeability of nitroxides.
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DOI：
10.1016/0167-4889(86)90073-x
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发表时间：
1986-08
期刊：
影响因子：
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通讯作者：
H. Swartz;M. Sentjurc;P. D. Morse
中科院分区：
文献类型：
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作者：
H. Swartz;M. Sentjurc;P. D. Morse
为了更准确地解释使用氮氧化物的研究，并提高氮氧化物在细胞基础研究和体内核磁共振造影剂中的使用效率，我们已经启动了一项氮氧化物在生物系统中的分布和代谢的系统研究。总的来说，这些结果为氮氧化物和细胞之间相互作用的某些方面提供了一个合理连贯的画面。氮氧化物的还原似乎是一个细胞内的过程，因此影响还原速率的主要变量之一是氮氧化物进入细胞的能力。氮氧化物进入细胞表现出相当大的可变性，其范围从基本上不渗透（例如2,2,6,6-四甲基哌啶- n -氧-4-三甲胺）到与还原速率相当的速率（例如2,2,5,5-四甲基吡啶- n -氧-3-羧酸），再到非常快以至于在细胞内和细胞外区室之间完全平衡（例如temone）。氮氧化物上带电基团的存在似乎是影响它们进入细胞能力的重要变量。一旦氮氧化物进入细胞，氮氧化物的结构，如哌啶环与吡咯烷环，是影响还原速率的主要因素。还原速率随着氮氧化物浓度的增加而增加。这表明主要的还原机制在我们所研究的浓度范围内不饱和。我们观察到在我们所研究的细胞和氮氧化物的整个浓度范围内，还原速率没有突然变化，这表明氮氧化物还原的机制没有改变。氧气的存在降低了观察到的许多氮氧化物的还原速率，这种影响与氮氧化物的浓度无关。
In order to interpret more accurately studies that have used nitroxides and to improve the efficacy of the use of nitroxides in both basic studies of cells and as contrast agents for in vivo NMR, we have initiated a systematic study of the distribution and metabolism of nitroxides in biological systems. Overall, the results provide a reasonably coherent picture of some aspects of the interactions between nitroxides and cells. Reduction of the nitroxides appears to be an intracellular process, so that one of the principal variables that affects the rate of reduction is the ability of a nitroxide to enter cells. The entrance of nitroxides into cells shows considerable variability and ranges from essentially no penetration (e.g., 2,2,6,6-tetramethylpiperidine-N-oxyl-4-trimethylamine) through rates that are comparable to rates of reduction (e.g., 2,2,5,5-tetramethylpyrrolidine-N-oxyl-3-carboxylic acid), to rates that are so fast that there is complete equilibrium between intracellular and extracellular compartments (e.g., Tempone). The presence of a charged group on the nitroxide appears to be the important variable that affects their ability to enter cells. Once a nitroxides enters the cell, the structure of the nitroxide, e.g., piperidine vs. pyrrolidine ring, is major factor that affects the rate of reduction. The rates of reduction increase with increasing concentrations of nitroxides. This indicates that the principal mechanism(s) of reduction do not saturate in the concentration range we studied. We observed no abrupt changes in the rates of reduction over the entire concentration range of cells and nitroxides that we studied, which suggests that the mechanism(s) of nitroxide reduction did not change. The presence of oxygen decreased the observed rate of reduction of many of the nitroxides and this effect was independent of the concentration of nitroxide.