Cysteine proteinase inhibitors block early steps in hemoglobin degradation by cultured malaria parasites
Cysteine proteinase inhibitors block early steps in hemoglobin degradation by cultured malaria parasites
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DOI：
10.1182/blood.v87.10.4448.bloodjournal87104448
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发表时间：
1996-05-15
期刊：
影响因子：
20.3
通讯作者：
Rosenthal, PJ
中科院分区：
文献类型：
--
作者：
deDominguez, NDG;Rosenthal, PJ
红细胞疟疾寄生虫降解血红蛋白作为寄生虫蛋白质合成的氨基酸来源。半胱氨酸蛋白酶抑制剂已被证明可以阻断培养的寄生虫对珠蛋白的水解，这表明疟疾的半胱氨酸蛋白酶是这一过程所必需的。在本研究中，我们已经评估了寄生虫蛋白酶在血红蛋白降解的早期步骤中的作用，即血红蛋白四聚体的解离和血红素与珠蛋白的分离。血红蛋白在疟疾食物泡的pH和还原条件下不自发变性或释放血红素，表明寄生虫酶活性对于血红蛋白降解的早期步骤是必需的。培养的寄生虫与半胱氨酸蛋白酶抑制剂一起孵育抑制血红蛋白的变性和血红素从珠蛋白的释放。这些结果表明，除了在珠蛋白水解中的作用外，疟疾半胱氨酸蛋白酶参与血红蛋白四聚体的解离和血红素从珠蛋白的释放。因此，疟疾半胱氨酸蛋白酶是一个有前途的抗疟化疗的目标。(C)1996年，美国血液学会。
Erythrocytic malaria parasites degrade hemoglobin as a source of amino acids for parasite protein synthesis. Cysteine proteinase inhibitors have been shown to block the hydrolysis of globin by cultured parasites, indicating that a malarial cysteine proteinase is required for this process. In the present study, we have evaluated the role of parasite proteinases in earlier steps of hemoglobin degradation, namely the dissociation of the hemoglobin tetramer and the separation of heme from globin. Hemoglobin did not spontaneously denature or release heme under the pH and reducing conditions of the malarial food vacuole, suggesting that parasite enzymatic activity is necessary for early steps in hemoglobin degradation, The incubation of cultured parasites with cysteine proteinase inhibitors inhibited the denaturation of hemoglobin and the release of heme from globin, These results suggest that, in addition to its role in globin hydrolysis, a malarial cysteine proteinase participates in the dissociation of the hemoglobin tetramer and the release of heme from globin. Thus, the malarial cysteine proteinase is a promising target for antimalarial chemotherapy. (C) 1996 by The American Society of Hematology.