Dubois V L, Platel D F, Pauly G, Tribouley-Duret J
Laboratoire d'Immunologie et Parasitologie, U.F.R. des Sciences Pharmaceutiques, Université de Bordeaux II, France.
Exp Parasitol. 1995 Aug;81(1):117-24. doi: 10.1006/expr.1995.1099.
Glutathione (GSH) plays a critical role in the detoxication and the protection of cells against oxidative stress. In the present study we examined the relationship between the intracellular GSH levels as well as glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx) activities and how they relate to Plasmodium berghei resistance to chloroquine. Resistant strains (CQR30 and CQR60) were selected in vivo from a sensitive strain (NK65). Marked increases in GSH levels and GST activity within resistant parasites were observed, compared to sensitive parasites. On the other hand, GR and GPx activities were similar in sensitive and resistant parasites. Treatment with chloroquine did not influence the intracellular level of GSH, but it was found to significantly decrease GR activity. Intracellular depletion of GSH, by a nontoxic concentration of buthionine sulfoximine (BSO), significantly sensitized the resistant parasites to chloroquine. These results suggest that the P. berghei resistance results from altered GSH and GST levels and activity, respectively, which enable the detoxification of chloroquine in resistant parasites.
谷胱甘肽（GSH）在解毒以及保护细胞免受氧化应激方面发挥着关键作用。在本研究中，我们检测了细胞内谷胱甘肽水平以及谷胱甘肽S-转移酶（GST）、谷胱甘肽还原酶（GR）和谷胱甘肽过氧化物酶（GPx）活性之间的关系，以及它们与伯氏疟原虫对氯喹的抗性之间的关联。抗性菌株（CQR30和CQR60）是从敏感菌株（NK65）体内筛选出来的。与敏感疟原虫相比，抗性疟原虫体内的谷胱甘肽水平和GST活性显著升高。另一方面，敏感和抗性疟原虫中的GR和GPx活性相似。氯喹处理并未影响细胞内谷胱甘肽水平，但发现其可显著降低GR活性。用无毒浓度的丁硫氨酸亚砜胺（BSO）使细胞内谷胱甘肽耗竭，可显著增强抗性疟原虫对氯喹的敏感性。这些结果表明，伯氏疟原虫的抗性分别源于谷胱甘肽和GST水平及活性的改变，这使得抗性疟原虫能够对氯喹进行解毒。
