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恶性疟原虫感染红细胞中游离钙和可交换钙的钙转运及区室分析

Calcium transport and compartment analysis of free and exchangeable calcium in Plasmodium falciparum-infected red blood cells.

作者信息

Kramer R, Ginsburg H

机构信息

Department of Biological Chemistry, Hebrew University of Jerusalem, Israel.

出版信息

J Protozool. 1991 Nov-Dec;38(6):594-601.

PMID:1667934
Abstract

Calcium (Ca2+) is indispensable for normal development of the various stages of the asexual erythrocytic cycle of malaria parasites. However, the mechanisms involved in Ca2+ uptake, compartmentalization and cellular regulation are poorly understood. To clarify some of these issues, we have measured total, exchangeable, and free Ca2+ in normal red cells (RBCs) and Plasmodium falciparum (FCR-3)-infected cells (IRBCs) as a function of parasite development. All three forms of Ca2+ were found to be substantially higher in IRBCs than in RBCs, and to increase with parasite maturation up to the trophozoite stage and decline thereafter. Exchangeable and free [Ca2+] in host cell and parasite compartments were determined by selectively lysing IRBCs with Sendai virus, and estimating these parameters in the lysate (host cytosol) and the pellet (parasite cytosol). Levels of both exchangeable and free [Ca2+] were found to be higher in host cytosol than in parasite cytosol. The Ca2+ gradient across the parasite membrane can be maintained by the pH gradient across this membrane by means of a Ca2+/H+ antiporter. Host cytosol free [Ca2+] reached levels known to produce structural, physiological and biochemical changes in RBCs, and could account for similar features normally seen in malaria-infected red cells. Uptake of Ca2+ into IRBCs was nonsaturable and substantially faster than the saturable Ca2+ uptake into RBCs. The rate of Ca2+ uptake across the parasite membrane was even faster suggesting that the rate-limiting step in uptake into intact IRBCs is the translocation of Ca2+ across the host cell membrane.

摘要

钙(Ca2+)对于疟原虫无性红细胞周期各个阶段的正常发育不可或缺。然而,参与Ca2+摄取、区室化和细胞调节的机制却鲜为人知。为了阐明其中的一些问题,我们测量了正常红细胞(RBCs)和恶性疟原虫(FCR-3)感染细胞(IRBCs)中总钙、可交换钙和游离钙随寄生虫发育的变化情况。结果发现,IRBCs中这三种形式的钙含量均显著高于RBCs,并且随着寄生虫成熟至滋养体阶段而增加,此后下降。通过用仙台病毒选择性裂解IRBCs,并估计裂解物(宿主细胞质)和沉淀(寄生虫细胞质)中的这些参数,来确定宿主细胞和寄生虫区室中可交换钙和游离[Ca2+]的水平。结果发现,宿主细胞质中可交换钙和游离[Ca2+]的水平均高于寄生虫细胞质。通过Ca2+/H+反向转运体,跨寄生虫膜的pH梯度可以维持跨该膜的Ca2+梯度。宿主细胞质游离[Ca2+]达到了已知会在RBCs中产生结构、生理和生化变化的水平,这可以解释疟疾感染红细胞中通常出现的类似特征。Ca2+进入IRBCs的摄取是不饱和的,并且比Ca2+进入RBCs的饱和摄取速度快得多。跨寄生虫膜的Ca2+摄取速率甚至更快,这表明完整IRBCs摄取过程中的限速步骤是Ca2+跨宿主细胞膜的转运。

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