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疟原虫色素:血红素解毒后的废物?

Hemozoin: a waste product after heme detoxification?

作者信息

Sun Jun, Fang Chuantao, Qin Xixi, Si Wenwen, Wang Fei, Li Yanna, Yan Xiaoli

机构信息

School of Medicine, Tongji University, 500 Zhennan Road, Shanghai, 200331, People's Republic of China.

Shanghai Tenth People's Hospital, Tenth peoples hospital of Tongji university, Shanghai, People's Republic of China, Shanghai, China.

出版信息

Parasit Vectors. 2025 Mar 4;18(1):83. doi: 10.1186/s13071-025-06699-x.

DOI:10.1186/s13071-025-06699-x
PMID:40038801
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11881329/
Abstract

BACKGROUND

Hemozoin is considered a waste byproduct of heme detoxification following hemoglobin digestion; consequently, the biological functions of hemozoin in hemozoin-producing organisms have often been overlooked. However, recent findings indicate that Schistosoma hemozoin facilitates the transfer of iron from erythrocytes to eggs through its formation and degradation, thereby increasing interest in the role of malarial hemozoin.

METHODS

Using transmission electron microscopy, we compared the formation of Schistosoma hemozoin and malaria hemozoin. Through transcriptome analysis of different stages of P. falciparum 3D7 and P. falciparum 3D7,- where the latter serves as a control with reduced hemozoin production, -we analyzed expression patterns of genes related to DNA synthesis, iron, and heme utilization. Using light microscopy, we observed hemozoin aggregation following artemether treatment, and macrophage morphology after ingesting hemozoin in vivo and in vitro.

RESULTS

Similar to Schistosoma hemozoin, malaria hemozoin consists of heme aggregation and a lipid matrix, likely involved in lipid processing and the utilization of heme and iron. Transcriptome analysis reveals that during the trophozoite stage, the expression levels of these genes in P. falciparum 3D7 and P. falciparum 3D7C580Y are higher than those during the schizont stage. Correspondingly, less hemozoin was detected at the trophozoite stage, while more was observed during the schizont stage. These results suggest that when more heme and iron are utilized, less heme is available for hemozoin formation. Conversely, when less heme and iron are utilized, they can accumulate for hemozoin formation during the schizont stage, likely benefiting lipid remodeling. Disruption of heme utilization and hemozoin aggregation may lead to parasite death. In addition, the hemozoin released by schizonts can impair macrophage functions, potentially protecting merozoites from phagocytosis. Furthermore, it may be carried by gametocytes into the next host, fulfilling their requirements for iron and heme during their development in mosquitoes.

CONCLUSIONS

Hemozoin is not a waste byproduct of heme detoxification but instead plays a crucial role in the parasite's life cycle.

摘要

背景

疟原虫色素被认为是血红蛋白消化后血红素解毒的一种废弃副产物;因此,疟原虫色素在产生疟原虫色素的生物体中的生物学功能常常被忽视。然而,最近的研究结果表明,血吸虫疟原虫色素通过其形成和降解促进铁从红细胞向虫卵的转移,从而增加了人们对疟原虫疟原虫色素作用的兴趣。

方法

使用透射电子显微镜,我们比较了血吸虫疟原虫色素和疟原虫疟原虫色素的形成。通过对恶性疟原虫3D7和恶性疟原虫3D7C580Y不同阶段的转录组分析(后者作为疟原虫色素产生减少的对照),我们分析了与DNA合成、铁和血红素利用相关基因的表达模式。使用光学显微镜,我们观察了蒿甲醚处理后疟原虫色素的聚集情况,以及巨噬细胞在体内和体外摄取疟原虫色素后的形态。

结果

与血吸虫疟原虫色素类似,疟原虫疟原虫色素由血红素聚集物和脂质基质组成,可能参与脂质加工以及血红素和铁的利用。转录组分析显示,在滋养体阶段,恶性疟原虫3D7和恶性疟原虫3D7C580Y中这些基因的表达水平高于裂殖体阶段。相应地,在滋养体阶段检测到的疟原虫色素较少,而在裂殖体阶段观察到的较多。这些结果表明,当更多的血红素和铁被利用时,可用于疟原虫色素形成的血红素就较少。相反,当较少的血红素和铁被利用时,它们可以在裂殖体阶段积累用于疟原虫色素形成,这可能有利于脂质重塑。血红素利用和疟原虫色素聚集的破坏可能导致寄生虫死亡。此外,裂殖体释放的疟原虫色素会损害巨噬细胞功能,可能保护裂殖子不被吞噬。此外,它可能被配子体携带到下一个宿主中,满足它们在蚊子体内发育过程中对铁和血红素的需求。

结论

疟原虫色素不是血红素解毒的废弃副产物,而是在寄生虫的生命周期中起着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6369/11881329/e9576e1d024d/13071_2025_6699_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6369/11881329/8eb3ba823291/13071_2025_6699_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6369/11881329/e9576e1d024d/13071_2025_6699_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6369/11881329/8eb3ba823291/13071_2025_6699_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6369/11881329/c9f7ebca88ac/13071_2025_6699_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6369/11881329/5bf4ec1f2a88/13071_2025_6699_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6369/11881329/dbd65c09c958/13071_2025_6699_Fig4_HTML.jpg
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