An in vitro study on the differentiated metabolic mechanism of chloroquine-resistant Plasmodium falciparum using high-resolution metabolomics

Jinhyuk Na; Jian Zhang; Young Lan Choe; Chae Seung Lim; Youngja Hwang Park

doi:10.1080/15287394.2021.1944945

An in vitro study on the differentiated metabolic mechanism of chloroquine-resistant Plasmodium falciparum using high-resolution metabolomics

Jinhyuk Na, Jian Zhang, Young Lan Choe, Chae Seung Lim, Youngja Hwang Park

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Chloroquine (CQ) is an important drug used therapeutically for treatment of malaria. However, due to limited number of studies on metabolic targets of chloroquine (CQ), it is difficult to attribute mechanisms underlying resistance associated with usage of this drug. The present study aimed to investigate the metabolic signatures of CQ-resistant Plasmodium falciparum (PfDd2) compared to CQ-sensitive Plasmodium falciparum (Pf3D7). Both Pf3D7 and PfDd2 were treated with CQ at 200 nM for 48 hr; thereafter, the harvested red blood cells (RBCs) and media were subjected to microscopy and high-resolution metabolomics (HRM). Glutathione, γ-L-glutamyl-L-cysteine, spermidine, inosine monophosphate, alanine, and fructose-1,6-bisphosphate were markedly altered in PfDd2 of RBC. In the media, cysteine, cysteic acid, spermidine, phenylacetaldehyde, and phenylacetic acid were significantly altered in PfDd2. These differential metabolic signatures related signaling pathways of PfDd2, such as oxidative stress pathway and glycolysis may provide evidence for understanding the resistance mechanism and pathogenesis of the CQ-resistant parasite.

Original language	English
Pages (from-to)	859-874
Number of pages	16
Journal	Journal of Toxicology and Environmental Health - Part A: Current Issues
Volume	84
Issue number	21
DOIs	https://doi.org/10.1080/15287394.2021.1944945
Publication status	Published - 2021

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (Grant Numbers NRF-2017R1A2B4003890, NRF-2017M3A9F1031229, and NRF-2020R1A2C2103067). The authors thank Dr. Karan Uppal and Dr. Shuzhao Li from the Emory University School of Medicine (Atlanta, GA, USA) for providing the R-package used to run the apLCMS and xMSannotator. The author declare that Prof. Eun-Taek Han provided PfDd2 and Pf3D7 strains.

Publisher Copyright:
© 2021 Taylor & Francis.

Keywords

chloroquine
high resolution metabolomics
Malaria
red blood cells
resistance

ASJC Scopus subject areas

Toxicology
Health, Toxicology and Mutagenesis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/15287394.2021.1944945

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An in vitro study on the differentiated metabolic mechanism of chloroquine-resistant Plasmodium falciparum using high-resolution metabolomics. / Na, Jinhyuk; Zhang, Jian; Choe, Young Lan et al.
In: Journal of Toxicology and Environmental Health - Part A: Current Issues, Vol. 84, No. 21, 2021, p. 859-874.

Research output: Contribution to journal › Article › peer-review

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abstract = "Chloroquine (CQ) is an important drug used therapeutically for treatment of malaria. However, due to limited number of studies on metabolic targets of chloroquine (CQ), it is difficult to attribute mechanisms underlying resistance associated with usage of this drug. The present study aimed to investigate the metabolic signatures of CQ-resistant Plasmodium falciparum (PfDd2) compared to CQ-sensitive Plasmodium falciparum (Pf3D7). Both Pf3D7 and PfDd2 were treated with CQ at 200 nM for 48 hr; thereafter, the harvested red blood cells (RBCs) and media were subjected to microscopy and high-resolution metabolomics (HRM). Glutathione, γ-L-glutamyl-L-cysteine, spermidine, inosine monophosphate, alanine, and fructose-1,6-bisphosphate were markedly altered in PfDd2 of RBC. In the media, cysteine, cysteic acid, spermidine, phenylacetaldehyde, and phenylacetic acid were significantly altered in PfDd2. These differential metabolic signatures related signaling pathways of PfDd2, such as oxidative stress pathway and glycolysis may provide evidence for understanding the resistance mechanism and pathogenesis of the CQ-resistant parasite.",

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An in vitro study on the differentiated metabolic mechanism of chloroquine-resistant Plasmodium falciparum using high-resolution metabolomics

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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