Spiteller G
Department of Organic Chemistry, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany.
Exp Gerontol. 2001 Sep;36(9):1425-57. doi: 10.1016/s0531-5565(01)00131-0.
Aging is related with an increase in oxidation products derived from nucleic acids, sugars, sterols and lipids. Evidence will be presented that these different oxidation products are generated by processes induced by changes in the cell membrane structure (CMS), and not by superoxide, as commonly assumed. CMS activate apparently membrane bound phospholipases A2 in mammals and plants. Such changes occur by proliferation, aging and especially by wounding. After activation of phospholipases, influx of Ca2+ ions and activation of lipoxygenases (LOX) is induced. The LOX transform polyunsaturated fatty acids (PUFAs) into lipid hydroperoxides (LOOHs), which seem to be decomposed by action of enzymes to signalling compounds. Following severe cell injury, LOX commit suicide. Their suicide liberates iron ions that induce nonenzymic lipid peroxidation (LPO) processes by generation of radicals. Radicals attack all compounds with the structural element -CH=CH-CH(2)-CH=CH-. Thus, they act on all PUFAs independently either in free or conjugated form. The most abundant LPO products are derived from linoleic acid. Radicals induce generation of peroxyl radicals, which oxidise a great variety of biological compounds including proteins and nucleic acids. Nonenzymic LPO processes are induced artificially by the treatment of pure PUFAs with bivalent metal ions. The products are separable after appropriate derivatisation by gas chromatography (GC). They are identified by electron impact mass spectrometry (EI/MS). The complete spectrum of LPO products obtained by artificial LPO of linoleic acid is detectable after wounding of tissue, in aged individuals and in patients suffering from age-dependent diseases. Genesis of different LPO products derived from linoleic acid will be discussed in detail. Some of the LPO products are of high chemical reactivity and therefore escape detection in biological surrounding. For instance, epoxides and highly unsaturated aldehydic compounds that apparently induce apoptosis.
衰老与源自核酸、糖类、固醇和脂质的氧化产物增加有关。将展示证据表明，这些不同的氧化产物是由细胞膜结构变化（CMS）诱导的过程产生的，而非如通常所认为的由超氧化物产生。CMS在哺乳动物和植物中显然会激活膜结合的磷脂酶A2。这种变化通过增殖、衰老尤其是创伤发生。磷脂酶激活后，会诱导Ca2+离子内流和脂氧合酶（LOX）激活。LOX将多不饱和脂肪酸（PUFA）转化为脂质氢过氧化物（LOOH），这些脂质氢过氧化物似乎会被酶作用分解为信号化合物。在严重细胞损伤后，LOX会自我毁灭。它们的自我毁灭会释放铁离子，这些铁离子通过产生自由基诱导非酶促脂质过氧化（LPO）过程。自由基攻击所有具有-CH=CH-CH(2)-CH=CH-结构元素的化合物。因此，它们独立作用于所有游离或共轭形式的PUFA。最丰富的LPO产物源自亚油酸。自由基诱导过氧自由基的产生，过氧自由基会氧化包括蛋白质和核酸在内的多种生物化合物。通过用二价金属离子处理纯PUFA可人工诱导非酶促LPO过程。经过适当衍生化后，产物可通过气相色谱（GC）分离。它们通过电子轰击质谱（EI/MS）进行鉴定。在组织受伤后、老年个体以及患有与年龄相关疾病的患者中，均可检测到通过亚油酸人工LPO获得的完整LPO产物谱。将详细讨论源自亚油酸的不同LPO产物的生成。一些LPO产物具有高化学反应性，因此在生物环境中难以检测到。例如，显然会诱导细胞凋亡的环氧化物和高度不饱和醛类化合物。
