G418 induces programmed cell death in Acanthamoeba through the elevation of intracellular calcium and cytochrome c translocation.


Journal

Parasitology research
ISSN: 1432-1955
Titre abrégé: Parasitol Res
Pays: Germany
ID NLM: 8703571

Informations de publication

Date de publication:
Feb 2019
Historique:
received: 22 10 2018
accepted: 19 12 2018
pubmed: 9 1 2019
medline: 16 3 2019
entrez: 9 1 2019
Statut: ppublish

Résumé

Acanthamoeba is a widely distributed opportunistic parasite which causes a vision-threatening keratitis and a life-threatening encephalitis. The cyst stage of this amoeba is especially resistant to currently used therapeutics and so alternative agents are urgently required. Growing evidence supports the existence of a programmed cell death system (PCD) in Acanthamoeba and while some features are shared by higher eukaryote cells, others differ. It is hoped that by understanding these differences we can exploit them as targets for novel drug intervention to activate PCD pathways in the amoebae but not the invaded human tissue. Here, we use the aminoglycoside G418 to activate PCD in Acanthamoeba. This drug caused a shape change in the treated amoebae. Cells rounded up and contracted, and after 6 h fragments of cells resembling the 'apoptotic bodies' of vertebrate cells were observed. G418 causes an increase in intracellular calcium from a resting level of 24 nM to 60 nM after 6 h of treatment. Mitochondrial function as assayed by the ΔΨ

Identifiants

pubmed: 30617503
doi: 10.1007/s00436-018-6192-0
pii: 10.1007/s00436-018-6192-0
pmc: PMC6349814
doi:

Substances chimiques

Amebicides 0
Gentamicins 0
Cytochromes c 9007-43-6
antibiotic G 418 A08F5XTI6G
Calcium SY7Q814VUP

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

641-651

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Auteurs

Zisis Koutsogiannis (Z)

Centre for Discovery Brain Sciences, Edinburgh, UK.

Ewan T MacLeod (ET)

Division of Infection and Pathway Medicine, Biomedical Sciences, Edinburgh Medical School, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, Scotland, EH8 9XD, UK.

Sutherland K Maciver (SK)

Centre for Discovery Brain Sciences, Edinburgh, UK. smaciver@ed.ac.uk.

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