Onukwufor 2013 J Exp Biol: Difference between revisions
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{{Publication | {{Publication | ||
|title=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 [Epub ahead of print]. ย | |title=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 [Epub ahead of print]. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/24265424 PMID: 24265424] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/24265424 PMID: 24265424] | ||
|authors=Onukwufor JO, Macdonald N, Kibenge F, Stevens D, Kamunde C | |authors=Onukwufor JO, Macdonald N, Kibenge F, Stevens D, Kamunde C | ||
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|journal=J Exp Biol | |journal=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 ยตM) 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 (โค 5 ยตM) 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. | |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 ยตM) 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 (โค 5 ยตM) 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=Hypoxia, Reoxygenation, Cadmium, Interactions, 5 Mitochondrial Bioenergetics, Reactive oxygen species (ROS), Proton leak, Fish | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|additional= | |area=Respiration | ||
|taxonomic group=Fishes | |||
|tissues=Liver | |||
|preparations=Isolated Mitochondria | |||
|injuries=Hypoxia | |||
|couplingstates=LEAK, OXPHOS, ETS | |||
|substratestates=CI | |||
|additional=[Epub ahead of print] | |||
}} | }} |
Revision as of 18:14, 16 December 2013
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 [Epub ahead of print]. |
Onukwufor JO, Macdonald N, Kibenge F, Stevens D, Kamunde C (2013) 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 ยตM) 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 (โค 5 ยตM) 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. โข Keywords: Hypoxia, Reoxygenation, Cadmium, Interactions, 5 Mitochondrial Bioenergetics, Reactive oxygen species (ROS), Proton leak, Fish
Labels: MiParea: Respiration
Stress:Hypoxia
Tissue;cell: Liver Preparation: Isolated Mitochondria"Isolated Mitochondria" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property.
Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
[Epub ahead of print]