Shi Xiaoyu, Wei Meng, Xu Zihao, Liu Ying, Zhang Mujia, Lv Li, Wang Qian
Department of Immunology, School of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, China.
Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.
Front Cell Dev Biol. 2021 May 11;9:639944. doi: 10.3389/fcell.2021.639944. eCollection 2021.
During the erythrocytic cycle, glucose is taken up by glucose transporters (GLUTs) in red blood cells (RBCs) and supplied to parasites via the hexose transporter. Here, we demonstrate that the glucose uptake pathway in infected RBCs (iRBCs) can be hijacked by vitamin C (Vc). GLUTs preferentially transport the oxidized form of Vc, which is subsequently reduced in the cytosol. Vc, which is expected to burden the intracellular reducing capacity, inhibits and growth. Vc uptake is drastically increased in iRBCs, with a large proportion entering parasites. Increased absorption of Vc causes accumulation of reactive oxygen species, reduced ATP production, and elevated eryptosis in iRBCs and apoptosis in parasites. The level of oxidative stress induced by Vc is significantly higher in iRBCs than uninfected RBCs, not seen in chloroquine or artemisinin-treated iRBCs, and effective in inhibiting chloroquine or artemisinin-resistant parasites. These findings provide important insights into the drug sensitivity of .
在红细胞内期，葡萄糖通过红细胞（RBC）中的葡萄糖转运蛋白（GLUTs）被摄取，并通过己糖转运蛋白供应给疟原虫。在此，我们证明感染红细胞（iRBCs）中的葡萄糖摄取途径可被维生素C（Vc）劫持。GLUTs优先转运Vc的氧化形式，其随后在细胞质中被还原。预计会加重细胞内还原能力负担的Vc会抑制疟原虫的生长。iRBCs中Vc的摄取大幅增加，其中很大一部分进入疟原虫。Vc吸收增加会导致活性氧的积累、ATP生成减少以及iRBCs中红细胞凋亡增加和疟原虫凋亡。Vc诱导的氧化应激水平在iRBCs中显著高于未感染的RBCs，在氯喹或青蒿素处理的iRBCs中未见此现象，且对抑制氯喹或青蒿素耐药的疟原虫有效。这些发现为疟原虫的药物敏感性提供了重要见解。
