Please use this identifier to cite or link to this item:
https://scholarbank.nus.edu.sg/handle/10635/243077
Title: | CELLULAR AND IMMUNOLOGICAL CONSEQUENCES OF DRUG-INDUCED CALCIUM DISTRIBUTION IN MALARIA-INFECTED ERYTHROCYTES | Authors: | CLAUDIA CARRERA BRAVO | ORCID iD: | orcid.org/0000-0003-3566-9022 | Keywords: | Eryptosis, Plasmodium falciparum, chloroquine, extracellular vesicles, proteomics, host-parasite interaction | Issue Date: | 18-Jan-2023 | Citation: | CLAUDIA CARRERA BRAVO (2023-01-18). CELLULAR AND IMMUNOLOGICAL CONSEQUENCES OF DRUG-INDUCED CALCIUM DISTRIBUTION IN MALARIA-INFECTED ERYTHROCYTES. ScholarBank@NUS Repository. | Abstract: | In order to reach the objective set by WHO to decrease cases by 2030, antimalarial drugs with novel modes of action are required. Previously, a novel mechanism of action of chloroquine (CQ) was reported involving features of programmed cell death in the parasite, mainly characterized by calcium efflux from digestive vacuole permeabilization. Increased intracellular calcium induces suicidal death of erythrocytes also known as eryptosis. This study aimed to identify the hallmarks of eryptosis and the downstream cellular effects during CQ treatment in P. falciparum-iRBCs. Our results revealed increased phosphatidylserine exposure, cell shrinkage and membrane blebbing, delineating an eryptotic phenotype. Interestingly, we determined that CQ-treated iRBCs released extracellular vesicles (EVs) that were highly enriched in proteasome and ribosome protein clusters. This unique EV cargo did not influence parasite growth rate but might activate IFN signaling pathways mediated by IL-6 in THP-1-derived macrophages. Our findings shed new insights into a novel drug-induced cell death mechanism that targets the parasite and specific components of the infected host RBC. | URI: | https://scholarbank.nus.edu.sg/handle/10635/243077 |
Appears in Collections: | Ph.D Theses (Open) |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
PhD Thesis_Claudia Carrera Bravo_2023.pdf | 5.97 MB | Adobe PDF | OPEN | None | View/Download |
Google ScholarTM
Check
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.