title: Loss of pH control in Plasmodium falciparum parasites subjected to oxidative stress.
abstract: The intraerythrocytic malaria parasite is susceptible to oxidative stress and this may play a role in the mechanism of action of some antimalarial agents. Here we show that exposure of the intraerythrocytic malaria parasite to the oxidising agent hydrogen peroxide results in a fall in the intracellular ATP level and inhibition of the parasite's V-type H(+)-ATPase, causing a loss of pH control in both the parasite cytosol and the internal digestive vacuole. In contrast to the V-type H(+)-ATPase, the parasite's digestive vacuole H(+)-pyrophosphatase is insensitive to hydrogen peroxide-induced oxidative stress. This work provides insights into the effects of oxidative stress on the intraerythrocytic parasite, as well as providing an alternative possible explanation for a previous report that light-induced oxidative stress causes selective lysis of the parasite's digestive vacuole.
authors.affiliation: Research School of Biology, The Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Donelly A
authors.initials: DA
authors.lastname: van Schalkwyk
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Saliba
authors.forename: Giancarlo A
authors.initials: GA
authors.lastname: Biagini
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Bray
authors.forename: Kiaran
authors.initials: K
authors.lastname: Kirk
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D043564:Inorganic Pyrophosphatase / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism
chemical_list: D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D025262:Vacuolar Proton-Translocating ATPases; D043564:Inorganic Pyrophosphatase
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