Difference between revisions of "Kupsch 2009 FEBS J"
(Created page with "{{Publication |title=Kupsch K, Hertel S, Kreutzmann P, Wolf G, Wallesch CW, Siemen D, Schönfeld P (2009) Impairment of mitochondrial function by minocycline. FEBS J. 276: 1729...") |
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depolarization and a decrease in state 3 as well as uncoupled | depolarization and a decrease in state 3 as well as uncoupled | ||
respiration. Swelling of RLM in KCl-based medium indicates that MC permeabilizes | respiration. Swelling of RLM in KCl-based medium indicates that MC permeabilizes | ||
the inner mitochondrial membrane (IMM) to K+ and Cl). This | the inner mitochondrial membrane (IMM) to K<sup>+</sup> and Cl). This | ||
view is supported by our findings that MC-induced swelling in the KClbased | view is supported by our findings that MC-induced swelling in the KClbased | ||
medium was partly suppressed by N,N¢-dicyclohexylcarbodiimide (an | medium was partly suppressed by N,N¢-dicyclohexylcarbodiimide (an | ||
inhibitor of IMM-linked K+-transport) and tributyltin (an inhibitor of the | inhibitor of IMM-linked K<sup>+</sup>-transport) and tributyltin (an inhibitor of the | ||
inner membrane anion channel) and that swelling was less pronounced | inner membrane anion channel) and that swelling was less pronounced | ||
when RLM were suspended in choline chloride-based medium. In addition, | when RLM were suspended in choline chloride-based medium. In addition, | ||
we observed a rapid MC-induced depletion of endogenous | we observed a rapid MC-induced depletion of endogenous Mg<sup>2+</sup> from | ||
RLM, an event that is known to activate ion-conducting pathways within | RLM, an event that is known to activate ion-conducting pathways within | ||
the IMM. Moreover, MC abolished the | the IMM. Moreover, MC abolished the Ca<sup>2+</sup> retention capacity of RLM | ||
irrespective of the incubation medium used, most likely by triggering permeability | irrespective of the incubation medium used, most likely by triggering permeability | ||
transition. In summary, we found that MC at low micromolar | transition. In summary, we found that MC at low micromolar | ||
concentrations impairs several energy-dependent functions of mitochondria | concentrations impairs several energy-dependent functions of mitochondria | ||
in vitro. | ''in vitro''. | ||
|keywords=Magnesium, Minocycline, Mitochondria, Neuroprotection, Permeability transition | |keywords=Magnesium, Minocycline, Mitochondria, Neuroprotection, Permeability transition | ||
}} | }} |
Revision as of 11:37, 2 November 2010
Kupsch K, Hertel S, Kreutzmann P, Wolf G, Wallesch CW, Siemen D, Schönfeld P (2009) Impairment of mitochondrial function by minocycline. FEBS J. 276: 1729–1738. |
Kupsch K, Hertel S, Kreutzmann P, Wolf G, Wallesch CW, Siemen D, Schoenfeld P (2009) FEBS J.
Abstract: There is an ongoing debate on the presence of beneficial effects of minocycline (MC), a tetracycline-like antibiotic, on the preservation of mitochondrial functions under conditions promoting mitochondria-mediated apoptosis. Here, we present a multiparameter study on the effects of MC on isolated rat liver mitochondria (RLM) suspended either in a KCl-based or in a sucrose-based medium. We found that the incubation medium used strongly affects the response of RLM to MC. In KCl-based medium, but not in sucrose-based medium, MC triggered mitochondrial swelling and cytochrome c release. MC-dependent swelling was associated with mitochondrial depolarization and a decrease in state 3 as well as uncoupled respiration. Swelling of RLM in KCl-based medium indicates that MC permeabilizes the inner mitochondrial membrane (IMM) to K+ and Cl). This view is supported by our findings that MC-induced swelling in the KClbased medium was partly suppressed by N,N¢-dicyclohexylcarbodiimide (an inhibitor of IMM-linked K+-transport) and tributyltin (an inhibitor of the inner membrane anion channel) and that swelling was less pronounced when RLM were suspended in choline chloride-based medium. In addition, we observed a rapid MC-induced depletion of endogenous Mg2+ from RLM, an event that is known to activate ion-conducting pathways within the IMM. Moreover, MC abolished the Ca2+ retention capacity of RLM irrespective of the incubation medium used, most likely by triggering permeability transition. In summary, we found that MC at low micromolar concentrations impairs several energy-dependent functions of mitochondria in vitro. • Keywords: Magnesium, Minocycline, Mitochondria, Neuroprotection, Permeability transition
Labels:
Stress:Cancer; Apoptosis; Cytochrome c"Cancer; Apoptosis; Cytochrome c" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Rat Tissue;cell: Hepatocyte; Liver"Hepatocyte; Liver" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property. 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.
Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property., Coupling; Membrane Potential"Coupling; Membrane Potential" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
HRR: Oxygraph-2k