Mitochondrial superoxide mediates heat-induced apoptotic-like death in Leishmania infantum.
Previous studies have shown that heat stress triggers a process of programmed cell death in Leishmania infantum promastigotes that resembles apoptosis in higher eukaryotes. Even though this cell death process takes about 40 h to be completed, several early changes in the heat-stressed cells can be observed. Hyperpolarization of the parasite mitochondrion is the earliest event detected, which correlates with an increase in respiration rates and a concomitant increase in superoxide radical production. Induction of oxidative stress seems to mediate the heat-induced cell death process, as indicated by the partial prevention of parasite death observed when cell cultures are supplemented with N-acetyl-cysteine or glutathione. These antioxidants are able to diminish the concentration of superoxide radical but they do not prevent mitochondrial hyperpolarization. Treatment of the heat stressed parasites with the inhibitors of the mitochondrial respiration TTFA, antimycin A and KCN significantly decreases the production of superoxide radicals, which confirms the mitochondrial origin of this reactive oxygen species.
Alzate
Juan F
JF
Departamento de Bioquímica y Biología Molecular, Campus Universitario, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.
Arias
Andrés A
AA
Moreno-Mateos
David
D
Alvarez-Barrientos
Alberto
A
Jiménez-Ruiz
Antonio
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D005434:Flow Cytometry; D018869:Heat-Shock Response; D018314:Leishmania infantum / Q000187:drug effects / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors
D000975:Antioxidants; D017382:Reactive Oxygen Species; D013481:Superoxides; D013482:Superoxide Dismutase; D010100:Oxygen