Bagnati M, Perugini C, Cau C, Bordone R, Albano E, Bellomo G
Department of Medical Sciences, University of Piemonte Orientale 'A. Avogadro', Novara, Italy.
Biochem J. 1999 May 15;340 ( Pt 1)(Pt 1):143-52.
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 pro-oxidant activity of uric acid, since this became apparent even when alpha-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.
在铜诱导的低密度脂蛋白（LDL）氧化过程中，将尿酸加入孵育培养基会产生抗氧化或促氧化作用。当在铜刺激的LDL氧化的抑制或延迟阶段后期以及随后的广泛传播阶段加入尿酸时，会出现促氧化作用，这表现为共轭二烯、脂质过氧化物、硫代巴比妥酸反应性物质的形成增加以及负电荷增加。尿酸的促氧化作用对铜诱导的LDL氧化具有特异性，并且需要以Cu（I）或Cu（II）形式存在的铜。此外，当铜与LDL的摩尔比低于约50的阈值时，这种促氧化作用会更加明显。在天然LDL中，抗氧化和促氧化活性之间的转变与铜促进的LDL氧化早期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会延迟尿酸促氧化活性的开始，并降低刺激的脂质过氧化速率。然而，先前耗尽α-生育酚并不是揭示尿酸促氧化活性的先决条件，因为即使LDL中仍大量存在α-生育酚（超过原始值的50%），这种促氧化活性也很明显。这些结果表明，无论内源性α-生育酚的水平如何，尿酸都可能通过将Cu（II）还原为Cu（I）来增强LDL氧化，从而使更多的Cu（I）可用于随后脂质过氧化物的自由基分解和传播反应。
