Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montréal, QC, Canada.
Exp Parasitol. 2010 Aug;125(4):315-24. doi: 10.1016/j.exppara.2010.02.009. Epub 2010 Feb 26.
In mice, loss of pantetheinase activity causes susceptibility to infection with Plasmodium chabaudi AS. Treatment of mice with the pantetheinase metabolite cysteamine reduces blood-stage replication of P. chabaudi and significantly increases survival. Similarly, a short exposure of Plasmodium to cysteamine ex vivo is sufficient to suppress parasite infectivity in vivo. This effect of cysteamine is specific and not observed with a related thiol (dimercaptosuccinic acid) or with the pantethine precursor of cysteamine. Also, cysteamine does not protect against infection with the parasite Trypanosoma cruzi or the fungal pathogen Candida albicans, suggesting cysteamine acts directly against the parasite and does not modulate host inflammatory response. Cysteamine exposure also blocks replication of P. falciparum in vitro; moreover, these treated parasites show higher levels of intact hemoglobin. This study highlights the in vivo action of cysteamine against Plasmodium and provides further evidence for the involvement of pantetheinase in host response to this infection.
在小鼠中,泛酰巯基乙胺酶活性的丧失会导致对疟原虫 chabaudi AS 的易感性。用泛酰巯基乙胺酶代谢物半胱胺治疗小鼠可降低疟原虫的血期复制,并显著提高存活率。同样,体外短时间接触半胱胺足以抑制体内寄生虫的感染力。半胱胺的这种作用是特异性的,与相关的硫醇(二巯基丁二酸)或半胱胺的泛酰巯基乙胺前体都没有观察到这种作用。此外,半胱胺不能预防寄生虫克氏锥虫或真菌病原体白色念珠菌的感染,这表明半胱胺直接作用于寄生虫,而不调节宿主炎症反应。半胱胺暴露也可阻断体外疟原虫 falciparum 的复制;此外,这些经过处理的寄生虫显示出更高水平的完整血红蛋白。本研究强调了半胱胺在体内对疟原虫的作用,并进一步证明了泛酰巯基乙胺酶参与宿主对这种感染的反应。