Zerda K S, Dresden M H, Chappell C L
Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030.
Exp Parasitol. 1988 Dec;67(2):238-46. doi: 10.1016/0014-4894(88)90071-9.
The adult stage of Schistosoma mansoni utilizes host hemoglobin as a nutrient source. A proteolytic enzyme (SMw32) that has "hemoglobinase" activity is secreted into the parasite gut where it appears to be rapidly activated by glutathione released from host red blood cells. In the present study the expression of this proteinase, in developing schistosomula, has been correlated with digestive tract development and a dramatic rise in enzyme activity as early as Days 8-10 of culture. No evidence of the SMw32 proteinase was found in eggs, cercariae, or in newly transformed larvae. Further, the proteinase expressed at Days 8-10 is indistinguishable from the adult worm enzyme. In the larvae, indirect immunofluorescence with an anti-SMw32 monoclonal antibody showed that the proteinase is found throughout the developing cecum. The importance of cysteine proteinases to parasite development was also studied using a specific enzyme inhibitor, Ep-459. In cultures containing Ep-459 most (75%) of the schistosomula failed to survive the 18-day study period. Moreover, those that did survive showed a decrease in their growth (body length). These data suggest that the SMw32 proteinase is a developmentally regulated enzyme and that cysteine proteinase activity is essential in providing nutrients for the growth and survival of this parasite in its mammalian host. Thus, this proteinase may be an important target for chemotherapeutic intervention.
曼氏血吸虫的成虫阶段利用宿主血红蛋白作为营养源。一种具有“血红蛋白酶”活性的蛋白水解酶（SMw32）被分泌到寄生虫肠道中，在那里它似乎会被宿主红细胞释放的谷胱甘肽迅速激活。在本研究中，这种蛋白酶在发育中的童虫中的表达与消化道发育相关，并且早在培养的第8 - 10天酶活性就急剧上升。在虫卵、尾蚴或新转化的幼虫中未发现SMw32蛋白酶的证据。此外，在第8 - 10天表达的蛋白酶与成虫酶无法区分。在幼虫中，用抗SMw32单克隆抗体进行间接免疫荧光显示，蛋白酶在整个发育中的盲肠中都有发现。还使用一种特异性酶抑制剂Ep - 459研究了半胱氨酸蛋白酶对寄生虫发育的重要性。在含有Ep - 459的培养物中，大多数（75%）童虫在18天的研究期内未能存活。此外，那些存活下来的童虫生长（体长）有所下降。这些数据表明，SMw32蛋白酶是一种受发育调控的酶，并且半胱氨酸蛋白酶活性对于该寄生虫在其哺乳动物宿主中的生长和存活提供营养至关重要。因此，这种蛋白酶可能是化疗干预的一个重要靶点。
