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Onukwufor 2013 J Exp Biol

From Bioblast
Publications in the MiPMap
Onukwufor JO, Macdonald N, Kibenge F, Stevens D, Kamunde C (2013) Hypoxia-cadmium interactions on rainbow trout (Oncorhynchus mykiss) mitochondrial bioenergetics: attenuation of hypoxia-induced proton leak by low doses of cadmium. J Exp Biol 217:831-40.

» PMID: 24265424 Open Access

Onukwufor JO, Macdonald N, Kibenge F, Stevens D, Kamunde C (2014) J Exp Biol

Abstract: The goal of the present study was to elucidate the modulatory effects of cadmium (Cd) on hypoxia-reoxygenation-induced mitochondrial dysfunction in light of the limited understanding of the mechanisms of multiple stressor interactions in aquatic organisms. Rainbow trout (Oncorhynchus mykiss) liver mitochondria were isolated and energized with complex I substrates, malate-glutamate, and exposed to hypoxia (0>PO2<2 torr) for 0-60 min followed by reoxygenation and measurement of coupled and uncoupled respiration and complex I enzyme activity. Thereafter, 5 min hypoxia was used to probe interactions with cadmium (Cd) (0-20 µM) and to test the hypothesis that deleterious effects of hypoxia-reoxygenation on mitochondria were mediated by reactive oxygen species (ROS). Hypoxia-reoxygenation inhibited state 3 and uncoupler-stimulated (state 3u) respiration while concomitantly stimulating state 4 and 4ol (proton leak) respirations, thus reducing phosphorylation and coupling efficiencies. Low doses of Cd (≤ 5 µM) reduced, while higher doses enhanced, hypoxia-stimulated proton leak. This was in contrast to the monotonic enhancement by Cd of hypoxia-reoxygenation-induced reductions of state 3 respiration, phosphorylation efficiency and coupling. Mitochondrial complex I activity was inhibited by hypoxia-reoxygenation, hence confirming the impairment of at least one component of the electron transport chain (ETC) in rainbow trout mitochondria. Similar to the effect on state 4 and proton leak, low doses of Cd partially reversed the hypoxia-reoxygenation-induced complex I activity inhibition. The ROS scavenger and sulfhydryl group donor, N-acetylcysteine (NAC), administrated immediately prior to hypoxia exposure, reduced hypoxia-reoxygenation-stimulated proton leak without rescuing the inhibited state 3 respiration suggesting that hypoxia-reoxygenation influences distinct aspects of mitochondria via different mechanisms. Our results indicate that hypoxia-reoxygenation impairs the ETC and sensitizes mitochondria to Cd via mechanisms that involve, at least in part, ROS. Moreover we provide, for the first time in fish, evidence for hormetic effect of Cd on mitochondrial bioenergetics -the attenuation of hypoxia-reoxygenation-stimulated proton leak and partial rescue of complex I inhibition by low Cd doses. Keywords: Cadmium, Fish, Hypoxia, Interactions, Mitochondrial bioenergetics, Proton leak, Reactive oxygen species (ROS), Reoxygenation

O2k-Network Lab: CA Charlottetown Kamunde C

Labels: MiParea: Respiration, Pharmacology;toxicology 

Stress:Ischemia-reperfusion, Oxidative stress;RONS, Hypoxia  Organism: Fishes  Tissue;cell: Liver  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS, ET  Pathway: