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Query: EC:1.9.3.1 (
cytochrome oxidase
)
8,822
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cultured astrocytes, activated to express the
inducible form
of nitric oxide synthase, produced up to 1 microM nitric oxide (NO) measured by a NO-selective electrode, while non-activated cells produced no detectable NO. The production of NO was associated with an inhibition of cellular respiration, measured simultaneously by an oxygen electrode. The inhibition of respiration was rapidly reversed by inhibiting the NO synthase or by binding the NO with haemoglobin. The respiratory inhibition had an NO, oxygen and substrate dependence consistent with NO-inhibition at
cytochrome oxidase
. This is the first demonstration that cells can reversibly inhibit mitochondrial respiration via NO production. This inhibition is large and potentially important in a range of pathophysiological conditions.
...
PMID:Nitric oxide produced by activated astrocytes rapidly and reversibly inhibits cellular respiration. 747 83
A macrophage cell line (J774), activated with interferon-gamma and endotoxin to express the
inducible form
of NO synthase (iNOS), immediately inhibited the cellular respiration of co-incubated L-929 fibroblasts or non-activated J774 macrophages. The inhibition was potent, rapid and reversible when the NO was removed by adding oxyhaemoglobin or by inhibiting iNOS. Exogenously added NO also rapidly and reversibly inhibited cellular respiration over the same range of NO concentrations. This inhibition was competitive with oxygen and due to direct inhibition of
cytochrome oxidase
. Thus, NO generated by one cell can regulate the respiration of adjacent cells, supporting the hypothesis that NO may be a physiological and/or pathological regulator of cellular respiration, via its inhibition of
cytochrome oxidase
.
...
PMID:Transcellular regulation of cell respiration by nitric oxide generated by activated macrophages. 984 46
Nitric oxide (NO) and its derivative, peroxynitrite (ONOO-), inhibit mitochondrial respiration, and this inhibition may contribute to both the physiological and cytotoxic actions of NO. Nanomolar concentrations of NO rapidly and reversibly inhibited
cytochrome oxidase
in competition with oxygen, as shown with isolated
cytochrome oxidase
, mitochondria, brain nerve terminals and cells. Cultured astrocytes and macrophages activated (by cytokines and endotoxin) to express the
inducible form
of NO synthase produced up to 1 microM NO, and inhibited their own respiration and that of co-incubated cells via reversible NO inhibition of
cytochrome oxidase
. NO-induced inhibition of respiration in brain nerve terminals resulted in rapid glutamate release, which might contribute to the neurotoxicity of NO. NO inhibition of
cytochrome oxidase
is reversible; however, incubation of cells with NO donors for 4 hours resulted in an inhibition of complex I, which was reversible by light and thiol reagents and may be due to nitrosylation of thiols in complex I. NO also caused the acute inhibition of catalase, stimulation of hydrogen peroxide production by mitochondria, and reaction with hydrogen peroxide on superoxide dismutase to produce peroxynitrite. Peroxynitrite inhibited complexes I, II and V (the ATP synthase), aconitase, creatine kinase, and increases the proton leak in isolated mitochondria. Peroxynitrite also caused opening of the permeability transition pore, resulting in the release of cytochrome c, which might then trigger apoptosis. Hypoxia/ischaemia also resulted in an acute reversible inhibition of
cytochrome oxidase
. Heart ischaemia caused the release of cytochrome c from mitochondria into the cytosol, and at the same time caspase-3-like-protease activity was activated in the cytoplasm. Addition of cytochrome c to non-ischaemic cytosol also caused activation of this protease activity, suggesting that caspase activation and consequent apoptosis is at least partly a result of this cytochrome c release.
...
PMID:Nitric oxide, cytochrome c and mitochondria. 1098 53
Products of inflammation and the activation of nitric oxide synthase have been proposed as a mechanism of oligodendrocyte injury in CNS inflammation. There are currently three well described and known isoforms of NOS. Of these, neuronal NOS (nNOS) was initially discovered in neurons, endothelial NOS (eNOS) in vascular endothelium, while the
inducible form
of NOS (iNOS) is known to be activated in oligodendrocytes, astrocytes and microglia. We examined the activation of nNOS and the down stream effects of NO production in oligodendrocyte precursor cells (OPC) and MO3.13 cell line following culture with LPS. Our studies show that both MO3.13 cells and OPC are susceptible to the cellular injury resulting from LPS mediated activation and NO production. Activation of the TLR4 receptor with LPS led to decrease in cell viability that was associated with loss of mitochondrial membrane potential and impaired enzymatic activity of complex I and
complex IV
protein of the respiratory chain. 7-NI, a known inhibitor of nNOS was able to rescue of cells from LPS mediated mitochondrial damage. Loss of mitochondrial function was associated with translocation of cytochrome C and apoptosis inducing factor to the cytosol, setting the stage for apoptosis. Phosphorylation of PI3K and Akt was required for optimal activation of NOS. These studies provide a biochemical basis for nNOS mediated oligodendrocyte injury and suggest similar mechanisms may play a role in diseases characterized by oligodendrocyte loss and demyelination.
...
PMID:nNOS mediated mitochondrial injury in LPS stimulated oligodendrocytes. 2228 18
