Drug-induced ER stress leads to induction of programmed cell death pathways of the malaria parasite

Unal S., Kina U. Y., Kamil M., Aly A. S. I., PALABIYIK B.

Parasitology Research, vol.123, no.7, 2024 (SCI-Expanded, Scopus) identifier identifier

  • Publication Type: Article / Article
  • Volume: 123 Issue: 7
  • Publication Date: 2024
  • Doi Number: 10.1007/s00436-024-08281-3
  • Journal Name: Parasitology Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: Apoptosis, Autophagy, ER stress, Malaria, Plasmodium
  • Bezmialem Vakıf University Affiliated: Yes

Abstract

The rapid emergence of drug resistance against the mainstream antimalarial drugs has increased the need for development of novel drugs. Recent approaches have embarked on the repurposing of existing drugs to induce cell death via programmed cell death pathways. However, little is known about the ER stress response and programmed cell death pathways of the malaria parasite. In this study, we treated ex vivo Plasmodium berghei cultures with tunicamycin, 5-fluorouracil, and chloroquine as known stress inducer drugs to probe the transcriptional changes of autophagy and apoptosis-related genes (PbATG5, PbATG8, PbATG12, and PbMCA2). Treatments with 5-fluorouracil and chloroquine resulted in the upregulation of all analyzed markers, yet the levels of PbATG5 and PbATG12 were dramatically higher in chloroquine-treated ex vivo cultures. In contrast, tunicamycin treatment resulted in the downregulation of both PbATG8 and PbATG12, and upregulation of PbMCA2. Our results indicate that the malaria parasite responds to various ER stressors by inducing autophagy- and/or apoptosis-like pathways.