Cytochrome-c oxidase isolated from the brain of swayback-diseased sheep displays unusual structure and uncharacteristic kinetics

1998 ◽  
Vol 34 (2-3) ◽  
pp. 233-247 ◽  
Author(s):  
Trevor Alleyne ◽  
Jerome Joseph ◽  
Anthony Lalla ◽  
Valerie Sampson ◽  
Andrew Adogwa
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Unusual Structure ◽  
The Brain

scholarly journals Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice

Science ◽  
2020 ◽  
Vol 368 (6491) ◽  
pp. 620-625 ◽  
Author(s):  
Liam M. Guthrie ◽  
Shivatheja Soma ◽  
Sai Yuan ◽  
Andres Silva ◽  
Mohammad Zulkifli ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Small Molecule ◽  
Murine Model ◽  
Copper Deficiency ◽  
Menkes Disease ◽  
Neurological Injury ◽  
Loss Of Function ◽  
Brindled Mouse ◽  
The Brain

Loss-of-function mutations in the copper (Cu) transporter ATP7A cause Menkes disease. Menkes is an infantile, fatal, hereditary copper-deficiency disorder that is characterized by progressive neurological injury culminating in death, typically by 3 years of age. Severe copper deficiency leads to multiple pathologies, including impaired energy generation caused by cytochrome c oxidase dysfunction in the mitochondria. Here we report that the small molecule elesclomol escorted copper to the mitochondria and increased cytochrome c oxidase levels in the brain. Through this mechanism, elesclomol prevented detrimental neurodegenerative changes and improved the survival of the mottled-brindled mouse—a murine model of severe Menkes disease. Thus, elesclomol holds promise for the treatment of Menkes and associated disorders of hereditary copper deficiency.

scholarly journals Assessing cerebral blood flow, oxygenation and cytochrome c oxidase stability in preterm infants during the first 3 days after birth

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Ajay Rajaram ◽  
Daniel Milej ◽  
Marianne Suwalski ◽  
Lilian Kebaya ◽  
Matthew Kewin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Preterm Infants ◽  
Near Infrared ◽  
Correlation Spectroscopy ◽  
The Impact ◽  
The Brain

AbstractA major concern with preterm birth is the risk of neurodevelopmental disability. Poor cerebral circulation leading to periods of hypoxia is believed to play a significant role in the etiology of preterm brain injury, with the first three days of life considered the period when the brain is most vulnerable. This study focused on monitoring cerebral perfusion and metabolism during the first 72 h after birth in preterm infants weighing less than 1500 g. Brain monitoring was performed by combining hyperspectral near-infrared spectroscopy to assess oxygen saturation and the oxidation state of cytochrome c oxidase (oxCCO), with diffuse correlation spectroscopy to monitor cerebral blood flow (CBF). In seven of eight patients, oxCCO remained independent of CBF, indicating adequate oxygen delivery despite any fluctuations in cerebral hemodynamics. In the remaining infant, a significant correlation between CBF and oxCCO was found during the monitoring periods on days 1 and 3. This infant also had the lowest baseline CBF, suggesting the impact of CBF instabilities on metabolism depends on the level of blood supply to the brain. In summary, this study demonstrated for the first time how continuous perfusion and metabolic monitoring can be achieved, opening the possibility to investigate if CBF/oxCCO monitoring could help identify preterm infants at risk of brain injury.

scholarly journals Nitric oxide and peroxynitrite exert distinct effects on mitochondrial respiration which are differentially blocked by glutathione or glucose

1996 ◽  
Vol 314 (3) ◽  
pp. 877-880 ◽  
Author(s):  
Ignacio LIZASOAIN ◽  
Maria A. MORO ◽  
Richard G. KNOWLES ◽  
Victor DARLEY-USMAR ◽  
Salvador MONCADA
Keyword(s):  
Nitric Oxide ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Mitochondrial Respiration ◽  
Submitochondrial Particles ◽  
Reversible Inhibition ◽  
The Brain ◽  
In Cells

Nitric oxide (NO) and peroxynitrite both inhibit respiration by brain submitochondrial particles, the former reversibly at cytochrome c oxidase, the latter irreversibly at complexes I–III. Both GSH (IC50 = 10 μM) and glucose (IC50 = 8 mM) prevented inhibition of respiration by peroxynitrite (ONOO-), but neither glucose (100 mM) nor GSH (100 μM) affected that by NO. Thus, unless ONOO- is formed within mitochondria it is unlikely to inhibit respiration in cells directly, because of reactions with cellular thiols and carbohydrates. However, the reversible inhibition of respiration at cytochrome c oxidase by NO is likely to occur (e.g. in the brain during ischaemia) and could be responsible for cytotoxicity.

scholarly journals Brain-Specific Serine-47 Modification of Cytochrome c Regulates Cytochrome c Oxidase Activity Attenuating ROS Production and Cell Death: Implications for Ischemia/Reperfusion Injury and Akt Signaling

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1843 ◽  
Author(s):  
Hasini A. Kalpage ◽  
Junmei Wan ◽  
Paul T. Morse ◽  
Icksoo Lee ◽  
Maik Hüttemann
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Reperfusion Injury ◽  
Cell Line ◽  
Cytochrome C Oxidase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ros Generation ◽  
Ros Production ◽  
The Brain

We previously reported that serine-47 (S47) phosphorylation of cytochrome c (Cytc) in the brain results in lower cytochrome c oxidase (COX) activity and caspase-3 activity in vitro. We here analyze the effect of S47 modification in fibroblast cell lines stably expressing S47E phosphomimetic Cytc, unphosphorylated WT, or S47A Cytc. Our results show that S47E Cytc results in partial inhibition of mitochondrial respiration corresponding with lower mitochondrial membrane potentials (ΔΨm) and reduced reactive oxygen species (ROS) production. When exposed to an oxygen-glucose deprivation/reoxygenation (OGD/R) model simulating ischemia/reperfusion injury, the Cytc S47E phosphomimetic cell line showed minimal ROS generation compared to the unphosphorylated WT Cytc cell line that generated high levels of ROS upon reoxygenation. Consequently, the S47E Cytc cell line also resulted in significantly lower cell death upon exposure to OGD/R, confirming the cytoprotective role of S47 phosphorylation of Cytc. S47E Cytc also resulted in lower cell death upon H2O2 treatment. Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain. Akt inhibitor wortmannin abolished S47 phosphorylation of Cytc, while the Akt activator SC79 maintained S47 phosphorylation of Cytc. Overall, our results suggest that loss of S47 phosphorylation of Cytc during brain ischemia drives reperfusion injury through maximal electron transport chain flux, ΔΨm hyperpolarization, and ROS-triggered cell death.

scholarly journals AMINOPHYLLINE REDUCES CYTOCHROME C OXIDASE IN THE BRAIN OF PREMATURE INFANTS

1992 ◽  
Vol 32 (5) ◽  
pp. 613-613
Author(s):  
Bucher Hans-Ulrich ◽  
Wolf Martin ◽  
Keel Matthias ◽  
Duc Gabriel
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Premature Infants ◽  
The Brain
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