Roberts L Jackson, Morrow J D
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232-6602, USA.
Cell Mol Life Sci. 2002 May;59(5):808-20. doi: 10.1007/s00018-002-8469-8.
We previously reported the discovery of prostaglandin F2-like compounds (F2-isoprostanes) formed by nonenzymatic free-radical-induced peroxidation of arachidonic acid. Quantification of F2-isoprostanes has proven to be a major advance in assessing oxidative stress status in vivo. Central in the pathway of formation of isoprostanes are prostaglandin H2-like endoperoxides, which also undergo rearrangement in vivo to form E-ring, D-ring, and thromboxane-ring compounds. E2- and D2-isoprostanes also undergo dehydration in vivo to form reactive cyclopentenone A2- and J2-isoprostanes, which are susceptible to Michael addition reactions with thiols. Recently, we described the formation of highly reactive gamma-ketoaldehydes (now termed isoketals) as products of isoprostane endoperoxide rearrangement which readily adduct to lysine residues on proteins and induce cross-links at rates that far exceed other aldehyde products of lipid peroxidation. Isoprostane-like compounds (neuroprostanes) and isoketal-like compounds (neuroketals) are formed from oxidation of docosahexaenoic acid, which is enriched in the brain, and measurement of neuroprostanes may provide a unique marker of oxidative neuronal injury.
我们之前报道了前列腺素F2样化合物（F2-异前列腺素）的发现，其由花生四烯酸的非酶自由基诱导过氧化反应形成。F2-异前列腺素的定量已被证明是评估体内氧化应激状态的一项重大进展。异前列腺素形成途径的核心是前列腺素H2样内过氧化物，其在体内也会重排形成E环、D环和血栓素环化合物。E2-和D2-异前列腺素在体内也会脱水形成具有反应活性的环戊烯酮A2-和J2-异前列腺素，它们易于与硫醇发生迈克尔加成反应。最近，我们描述了高反应性γ-酮醛（现称为异酮体）的形成，其作为异前列腺素内过氧化物重排的产物，很容易与蛋白质上的赖氨酸残基加合，并以远远超过脂质过氧化其他醛类产物的速率诱导交联。类异前列腺素化合物（神经前列腺素）和类异酮体化合物（神经酮体）由大脑中富含的二十二碳六烯酸氧化形成，神经前列腺素的测量可能提供氧化神经元损伤的独特标志物。
