Selkirk M E, Smith V P, Thomas G R, Gounaris K
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, U.K.
Int J Parasitol. 1998 Sep;28(9):1315-32. doi: 10.1016/s0020-7519(98)00107-6.
All filariae examined to date express a comprehensive repertoire of both cytoplasmic and secreted anti-oxidant enzymes, although significant differences exist between species and life-cycle stages. Adult Brugia malayi, Dirofilaria immitis and Onchocerca volvulus secrete CuZn superoxide dismutases, and the former two species also secrete a selenocysteine-independent glutathione peroxidase. This enzyme has been localised to the cuticular matrix of B. malayi, and the preferential reduction of fatty acid- and phospholipid hydroperoxides suggests that it may protect cuticular membranes from oxidative damage rather than directly metabolise hydrogen peroxide. Adult O. volvulus may compensate for an apparent deficiency in expression of this enzyme via a secreted variant of glutathione S-transferase. Recent studies have identified a highly expressed family of enzymes collectively termed peroxiredoxins, which most probably play an essential role in reduction of hydroperoxides. Data from cDNA cloning exercises indicate that all filarial species examined thus far express at least two peroxiredoxin variants which have been localised to diverse tissues. In-vitro studies have shown that B. malayi are particularly resistant to oxidative stress, and that the parasites do not rely solely on enzymatic mechanisms of defence. Cuticular lipids are relatively resistant to lipid peroxidation due to the low unsaturation indices of the constituent fatty acyl residues, but complete protection is afforded by the presence of alpha-tocopherol, presumably assimilated from host extracellular fluids. Brugia malayi are also relatively resistant to nitric oxide-mediated toxicity, and this may be due in part to incomplete dependence on aerobic metabolism. Little is known of potential mechanisms for detoxification of nitric oxide derivatives and adaptive responses to oxidative stress in general, and these represent goals for future research.
迄今为止所检测的所有丝虫均表达了一系列完整的胞质和分泌型抗氧化酶，尽管不同物种和生命周期阶段之间存在显著差异。马来布鲁线虫、犬恶丝虫和盘尾丝虫的成虫分泌铜锌超氧化物歧化酶，前两种还分泌一种不依赖硒代半胱氨酸的谷胱甘肽过氧化物酶。该酶已定位在马来布鲁线虫的表皮基质中，对脂肪酸和磷脂氢过氧化物的优先还原表明，它可能保护表皮膜免受氧化损伤，而不是直接代谢过氧化氢。盘尾丝虫成虫可能通过分泌型谷胱甘肽S-转移酶变体来弥补该酶表达的明显不足。最近的研究发现了一个高表达的酶家族，统称为过氧化物氧还蛋白，它们很可能在氢过氧化物的还原中起重要作用。来自cDNA克隆实验的数据表明，迄今为止所检测的所有丝虫物种均表达至少两种过氧化物氧还蛋白变体，这些变体已定位到不同组织中。体外研究表明，马来布鲁线虫对氧化应激具有特别的抗性，并且寄生虫并不完全依赖酶促防御机制。由于组成脂肪酸酰基残基的不饱和指数较低，表皮脂质对脂质过氧化相对具有抗性，但α-生育酚的存在提供了完全保护，α-生育酚大概是从宿主细胞外液中吸收的。马来布鲁线虫对一氧化氮介导的毒性也相对具有抗性，这可能部分归因于对有氧代谢的不完全依赖。关于一氧化氮衍生物的解毒潜在机制以及一般对氧化应激的适应性反应知之甚少，这些是未来研究的目标。
