When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid
When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid
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DOI：
10.1042/0264-6021:3400143
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发表时间：
1999-05-15
影响因子：
4.1
通讯作者：
Bellomo, G
中科院分区：
文献类型：
--
作者：
Bagnati, M;Perugini, C;Bellomo, G
在铜诱导的低密度脂蛋白（LDL）氧化过程中，孵育培养基中包含的尿酸具有抗氧化或促氧化作用。的促氧化剂的作用，反映了增强形成共轭二烯，脂质过氧化物，硫代巴比妥酸反应性物质和负电荷的增加，发生时，尿酸被添加到后期的抑制或滞后阶段，并在随后的广泛传播阶段的铜刺激的LDL氧化。尿酸的促氧化作用对铜诱导的LDL氧化是特异性的，并且需要铜以Cu（I）或Cu（II）的形式存在。此外，当铜与LDL的摩尔比低于约100的阈值时，其变得更加明显。50.在天然LDL中，抗氧化剂和促氧化剂活性之间的转变与铜促进LDL氧化的早期阶段形成的脂质氢过氧化物的可用性有关。用α-生育酚人工富集分离的LDL延迟了尿酸的促氧化活性的开始，并且也降低了刺激的脂质过氧化的速率。然而，先前α-生育酚的消耗不是揭示尿酸促氧化活性的先决条件，因为即使在LDL中仍存在大量α-生育酚（超过原始值的50%）时，这也变得明显。这些结果表明，无论内源性α-生育酚的水平如何，尿酸可能通过将Cu（II）还原为Cu（I）来增强LDL氧化，从而使更多的Cu（I）可用于随后的脂质过氧化物自由基分解和增殖反应。
The inclusion of uric acid in the incubation medium during copper-induced low-density lipoprotein (LDL) oxidation exerted either an antioxidant or pro-oxidant effect. The pro-oxidant effect, as mirrored by an enhanced formation of conjugated dienes, lipid peroxides, thiobarbituric acid-reactive substances and increase in negative charge, occurred when uric acid was added late during the inhibitory or lag phase and during the subsequent extensive propagation phase of copper-stimulated LDL oxidation. The pro-oxidant effect of uric acid was specific for copper-induced LDL oxidation and required the presence of copper as either Cu(I) or Cu(II). In addition, it became much more evident when the copper to LDL molar ratio was below a threshold value of approx. 50. In native LDL, the shift between the antioxidant and the pro-oxidant activities was related to the availability of lipid hydroperoxides formed during the early phases of copper-promoted LDL oxidation. The artificial enrichment of isolated LDL with alpha-tocopherol delayed the onset of the pro-oxidant activity of uric acid and also decreased the rate of stimulated lipid peroxidation. However, previous depletion of alpha-tocopherol was not a prerequisite for unmasking the prooxidant activity of uric acid, since this became apparent even when cc-tocopherol was still present in significant amounts (more than 50% of the original values) in LDL. These results suggest, irrespective of the levels of endogenous alpha-tocopherol, that uric acid may enhance LDL oxidation by reducing Cu(II) to Cu(I), thus making more Cu(I) available for subsequent radical decomposition of lipid peroxides and propagation reactions.