Orjih A U, Fitch C D
Department of Internal Medicine, Saint Louis University School of Medicine, MO 63104.
Biochim Biophys Acta. 1993 Jul 11;1157(3):270-4. doi: 10.1016/0304-4165(93)90109-l.
Synchronized Plasmodium falciparum parasites were grown in erythrocytic culture for measurement of malaria pigment (hemozoin) production using a simple method based on the insolubility of beta-hematin, the principal pigment of hemozoin. In the last 44 h of the life cycle, one strain (chloroquine-susceptible) incorporated an average of 960 pmol of ferriprotoporphyrin IX (FP) from hemoglobin into beta-hematin per 10(6) parasitized erythrocytes. By comparison, another strain (chloroquine-resistant) incorporated 515 pmol of FP into beta-hematin. When exposed to 25 ng of chloroquine per ml of culture medium, chloroquine-susceptible P. falciparum incorporated 240 pmol of FP into beta-hematin per 10(6) parasitized erythrocytes in one intraerythrocytic life cycle. In contrast chloroquine-resistant P. falciparum exposed to 100 ng of chloroquine per ml incorporated 630 pmol of FP into beta-hematin. Thus, chloroquine inhibits hemozoin production in chloroquine-susceptible P. falciparum but not in chloroquine-resistant P. falciparum. On the contrary, sublethal concentrations of chloroquine partially reverse a deficiency of hemozoin production in chloroquine-resistant P. falciparum. These results indicate that the adaptation responsible for chloroquine resistance in P. falciparum prevents the accumulation of toxic FP by preventing chloroquine from uncoupling the processes of hemoglobin degradation and hemozoin production.
同步培养的恶性疟原虫在红细胞培养物中生长，采用基于疟色素（疟原虫色素）主要成分β-血红素不溶性的简单方法来测量疟色素的产生。在生命周期的最后44小时，一个菌株（氯喹敏感株）每10⁶个被寄生的红细胞平均将960皮摩尔的血红蛋白铁原卟啉IX（FP）掺入β-血红素中。相比之下，另一个菌株（氯喹耐药株）将515皮摩尔的FP掺入β-血红素中。当每毫升培养基中加入25纳克氯喹时，氯喹敏感的恶性疟原虫在一个红细胞内生命周期中每10⁶个被寄生的红细胞将240皮摩尔的FP掺入β-血红素中。相比之下，每毫升加入100纳克氯喹的氯喹耐药恶性疟原虫将630皮摩尔的FP掺入β-血红素中。因此，氯喹抑制氯喹敏感的恶性疟原虫产生疟色素，但不抑制氯喹耐药的恶性疟原虫。相反，亚致死浓度的氯喹可部分逆转氯喹耐药的恶性疟原虫疟色素产生不足的情况。这些结果表明，恶性疟原虫中导致氯喹耐药的适应性变化通过阻止氯喹解偶联血红蛋白降解和疟色素产生的过程，从而防止了有毒FP的积累。
