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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >The pyrrolopyrimidine U101033E is a potent free radical scavenger and prevents Fe(II)-induced lipid peroxidation in synaptosomal membranes
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The pyrrolopyrimidine U101033E is a potent free radical scavenger and prevents Fe(II)-induced lipid peroxidation in synaptosomal membranes

机译：吡咯并嘧啶U101033E是有效的自由基清除剂，可防止滑膜中Fe（II）诱导的脂质过氧化

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The pyrrolopyrimidine U101033E is a therapeutic compound potentially useful in stroke, head injury and other oxidative stress conditions. Electron paramagnetic resonance (EPR) techniques of spin labeling and spin trapping in conjunction with measures of lipid and protein oxidation have been used to investigate the proposed antioxidant capacity of U101033E. We report potent antioxidant activity of this agent in aqueous cell-free solution as measured by spin trapping. U101033E significantly (P < 0.005) reduces the formation of the EPR active spin trap N-t-butyl-α-phenylnitrone (PBN)-radical adduct by 17.1% at a concentration of 1 μM, four orders of magnitude less than the concentration of PBN. As measured by the decrease in signal intensity of lipid-resident nitroxide stearate spin probes, an EPR assay for lipid peroxidation, this pyrrolopyrimidine compound efficiently protected against hydroxyl radical-induced lipid peroxidation in cortical synaptosomal membranes deep within the membrane bilayer, but not closer to the membrane surface. In addition, U101033E partially prevents synaptosomal protein oxidation in the presence of Fe(II); however, U101033E demonstrates some protein oxidative effects itself. These results are supportive of the proposed role of U101033E as a lipid-specific antioxidant, especially for protection against lipid peroxidation that occurs deep within the membrane bilayer, but raise some potential concerns about the oxidative nature of this agent toward proteins.
机译：吡咯并嘧啶U101033E是潜在用于中风，头部受伤和其他氧化应激状况的治疗性化合物。自旋标记和自旋俘获的电子顺磁共振（EPR）技术结合脂质和蛋白质氧化措施已用于研究拟议的U101033E的抗氧化能力。我们报告了该试剂在无细胞水溶液中的有效抗氧化活性，该值通过旋转捕获进行测量。在浓度为1μM时，U101033E显着（P <0.005）将EPR活性自旋阱N-叔丁基-α-苯基硝基（PBN）-自由基加合物的形成减少了17.1％，比PBN的浓度低四个数量级。通过脂质驻留型一氧化氮硬脂酸酯自旋探针的信号强度的降低（脂质过氧化的EPR测定）来测量，该吡咯并嘧啶化合物可有效保护膜层双层内深层但不更近的皮质突触体膜中的羟基自由基诱导的脂质过氧化。膜表面。此外，U101033E在Fe（II）存在下部分防止突触体蛋白氧化;但是，U101033E本身表现出某些蛋白质氧化作用。这些结果支持了U101033E作为脂质特异性抗氧化剂的拟议作用，尤其是对于防止在膜双层内部深处发生的脂质过氧化作用的保护，但引发了对该试剂对蛋白质氧化性质的某些潜在担忧。

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