myxothiazol and dihydroethidium

myxothiazol has been researched along with dihydroethidium* in 2 studies

Other Studies

2 other study(ies) available for myxothiazol and dihydroethidium

ArticleYear
Qo site of mitochondrial complex III is the source of increased superoxide after transient exposure to hydrogen peroxide.
    Journal of molecular and cellular cardiology, 2010, Volume: 49, Issue:5

    Transient exposure of cardiac myocytes to hydrogen peroxide (H(2)O(2)) results in further production of superoxide by the mitochondria as a result of increased influx of calcium through the L-type Ca(2+) channel and increased calcium uptake by the mitochondria. The response persists as a result of positive feedback on the channel and induces alterations in protein synthesis and cell size consistent with the development of myocyte hypertrophy. The aim of this study was to investigate the site of increased superoxide production within the mitochondria. Exposure of myocytes to 30 μM H(2)O(2) (5 min) then 10 U/mL catalase (5 min) increased dihydroethidium (DHE) signal by 58.7 ± 12.0% (n=4) compared to myocytes exposed to 0 μM H(2)O(2) for 5 min followed by 10 U/mL catalase (n=9). Complex I inhibitors DPI (n=5) and rotenone (n=7) attenuated the increase in DHE signal due to H(2)O(2). Complex III inhibitors myxothiazol (n=16) and stigmatellin (n=5) also attenuated the increase in DHE signal due to H(2)O(2). However, antimycin A (inhibitor of Q(i) site of complex III) had no effect. We "isolated" complex III in the intact cell by applying succinate in the patch pipette and exposing the cell to rotenone and antimycin A. Myxothiazol and TCA cycle inhibitors α-keto-β-methyl-n-valeric acid (KMV) and 4-hydroxynonenal (4-HNE) completely attenuated the increase in DHE signal. Direct activation of the L-type Ca(2+) channel by voltage-step mimicked the increase in DHE signal after transient exposure to H(2)O(2) (47.6 ± 17.8%, n=6) while intracellular application of catalase attenuated the increase in DHE signal due to H(2)O(2) (n=6). We propose that elevated superoxide production after transient exposure to H(2)O(2) occurs at the Q(o) superoxide generation site of complex III in cardiac myocytes and that an increase in TCA cycle activity plays a significant role in mediating the response.

    Topics: Aldehydes; Animals; Antimycin A; Calcium Channels, L-Type; Citric Acid Cycle; Electron Transport Complex III; Electron Transport Complex IV; Ethidium; Guinea Pigs; Hydrogen Peroxide; Ion Channel Gating; Membrane Potential, Mitochondrial; Methacrylates; Mitochondria; Myocytes, Cardiac; Polyenes; Reproducibility of Results; Rotenone; Superoxides; Thiazoles

2010
Participation of mitochondrial respiratory complex III in neutrophil activation and lung injury.
    American journal of physiology. Lung cellular and molecular physiology, 2009, Volume: 296, Issue:4

    Reactive oxygen species (ROS) produced during mitochondrial activity participate in the regulation of intracellular signaling pathways. However, there is only limited information concerning the role that ROS derived from the mitochondrial respiratory chain play in modulating neutrophil activity and participation in acute inflammatory processes. Because mitochondrial complex III is a major site of ROS formation, we examined whether selective complex III inhibition, through exposure of neutrophils to myxothiazol or antimycin A, would affect LPS-induced activation. Culture of neutrophils with antimycin A or myxothiazol resulted in increased intracellular levels of ROS, including superoxide and hydrogen peroxide (H(2)O(2)). Inhibition of complex III activity reduced LPS-induced degradation of IkappaB-alpha, nuclear accumulation of NF-kappaB, and proinflammatory cytokine production. The effects of antimycin A or myxothiazol appeared to be dependent on generation of H(2)O(2) since addition of pegylated catalase to neutrophils restored LPS-mediated IkappaB-alpha degradation and production of proinflammatory cytokines. Administration of myxothiazol to mice resulted in diminished mitochondrial complex III activity in the lungs and decreased severity of LPS-induced lung injury. These results indicate that inhibition of mitochondrial complex III diminishes Toll-like receptor 4-induced neutrophil activation through a mechanism dependent on H(2)O(2) generation and also reduces the severity of lung injury due to LPS exposure, a pathophysiologic process in which neutrophils play a major role.

    Topics: Animals; Antimycin A; Cell Nucleus; Cytokines; Electron Transport Complex III; Ethidium; Fluoresceins; I-kappa B Proteins; Lipopolysaccharides; Lung Injury; Male; Methacrylates; Mice; Mitochondria; Neutrophil Activation; Neutrophils; NF-kappa B; NF-KappaB Inhibitor alpha; Oxidation-Reduction; Protein Transport; Reactive Oxygen Species; Thiazoles

2009
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