Roberts L J, Brame C J, Chen Y, Morrow J D
Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA.
Methods Mol Biol. 1999;120:257-85. doi: 10.1385/1-59259-263-5:257.
The discovery of IsoPs has been an interesting development for a number of reasons, apart from the fact that it involves novel biochemistry. The simple fact that prostanoids are produced nonenzymatically in prodigous quantities in vivo and in much greater quantities than prostaglandins generated by the cyclooxygenase enzyme was a remarkable finding. The observation that detectable quantities of F2-IsoPs are present in all tissues and human biological fluids carries interesting implications. Previously, there had been little convincing evidence for the occurrence of lipid peroxidation in vivo except under unusual conditions of severe oxidative stress. However, the finding that F2-IsoPs can be easily detected in normal humans suggests a continuous level of ongoing oxidative injury that is not completely suppressed by the elaborate system of antioxidant defenses that have evolved. Another very important aspect of the discovery of IsoPs is that it has brought to the field a long sought after reliable approach to assess oxidative stress status in vivo. The continuing and expanded use of measurements of IsoPs for this purpose will contribute in a very valuable way to advancing our understanding of the role of free radicals in human disease processes. Further, the finding that these compounds are not simply markers of oxidant injury but can also exert potent biological actions both by interaction with specific receptors and, in the case of IsoLGs and cyclopentenenone IsoPs, by virtue of their chemical reactivity, has identified several new classes of molecules that are produced by free radical-induced lipid peroxidation that may mediate some of the adverse sequela of oxidant injury. The elucidation of the variety of compounds that are produced as products of the IsoP pathway and more recently the NP pathway provides vast new areas for scientific inquiry that should yield new and interesting information as this area continues to advance.
异前列腺素（IsoPs）的发现是一个有趣的进展，原因有很多，除了它涉及新的生物化学这一事实之外。一个简单的事实是，前列腺素在体内以非酶促方式大量产生，其数量比环氧化酶产生的前列腺素要多得多，这是一个显著的发现。在所有组织和人体生物体液中都存在可检测量的F2 - 异前列腺素这一观察结果具有有趣的意义。以前，除了在严重氧化应激的异常条件下，几乎没有令人信服的体内脂质过氧化发生的证据。然而，在正常人体内能够轻易检测到F2 - 异前列腺素这一发现表明，存在持续的氧化损伤水平，而进化而来的复杂抗氧化防御系统并不能完全抑制这种损伤。异前列腺素发现的另一个非常重要的方面是，它为该领域带来了一种长期寻求的可靠方法，用于评估体内的氧化应激状态。为此目的持续且扩大使用异前列腺素测量将以非常有价值的方式有助于推进我们对自由基在人类疾病过程中作用的理解。此外，这些化合物不仅是氧化损伤的标志物，而且还能通过与特定受体相互作用以及（就异链烯醛（IsoLGs）和环戊烯酮异前列腺素而言）凭借其化学反应性发挥强大的生物学作用，这一发现确定了几类由自由基诱导的脂质过氧化产生的新分子，它们可能介导氧化损伤的一些不良后果。对作为异前列腺素途径以及最近的硝基前列腺素（NP）途径产物产生的各种化合物的阐明为科学探究提供了广阔的新领域，随着该领域的不断发展，应该会产生新的有趣信息。
