Effect of N-acetyl-cysteine on the hypoxic ventilatory response and erythropoietin production: linkage between plasma thiol redox state and O(2) chemosensitivity.

@article{Hildebrandt2002EffectON,
  title={Effect of N-acetyl-cysteine on the hypoxic ventilatory response and erythropoietin production: linkage between plasma thiol redox state and O(2) chemosensitivity.},
  author={Wulf Hildebrandt and Steve Alexander and Peter B{\"a}rtsch and Wulf Dröge},
  journal={Blood},
  year={2002},
  volume={99 5},
  pages={
          1552-5
        }
}
Oxygen-sensing chemoreceptors contribute significantly to the regulation of the respiratory drive and arterial PO(2) levels. The hypoxic ventilatory response (HVR) decreases strongly with age and is modulated by prolonged hypoxia and physical exercise. Several earlier studies indicated that the regulation of the ventilatory response and erythropoietin (EPO) production by the respective oxygen sensors involves redox-sensitive signaling pathways, which are triggered by the O(2)-dependent… 

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References

SHOWING 1-10 OF 36 REFERENCES
S-Nitrosothiols signal the ventilatory response to hypoxia
TLDR
It is demonstrated that S-nitrosothiol biochemistry is of central importance to the regulation of breathing, and plasma from deoxygenated, but not from oxygenated, blood produces the ventilatory effect of both SNOs and hypoxia.
Role of hydrogen peroxide in hypoxia-induced erythropoietin production.
TLDR
The addition of exogenous H2O2 inhibited hypoxia-induced erythropoietin (Epo) production in the human hepatoma cell line HepG2 and supported the hypothesis that an H2 O2-generating haem protein might be part of the O2 sensor that controls Epo production.
Chemoreceptor discharges and cytochrome redox changes of the rat carotid body: role of heme ligands.
TLDR
It is hypothesized that carotid body type I cells and the apposed nerve endings use different mechanisms for oxygen sensing: the nerve endings generate action potentials in association with membrane heme proteins whereas cytosolic hemeprotein signal the redox state, releasing modulators or transmitters from type I Cells.
Oxygen sensing and molecular adaptation to hypoxia.
TLDR
Redox chemistry appears to play a critical role both in the trans-activation of oxygen-responsive genes in unicellular organisms as well as in the activation of HIF-1, which is required for the hypoxic induction of physiologically important genes.
Differential reconstitution of mitochondrial respiratory chain activity and plasma redox state by cysteine and ornithine in a model of cancer cachexia.
TLDR
The studies on the effects of ornithine, cysteine, and N-acetyl-cysteine (NAC) illuminate some of the mechanistic pathways involved in cachexia and suggest targets for therapeutic intervention.
Effects of aging on ventilatory and occlusion pressure responses to hypoxia and hypercapnia.
TLDR
It was found that ventilatory responses to both hypercapnia and hypoxia were reduced in the elderly by approximately 50%.
The role of N-acetylcystein administration on the oxidative response of neutrophils during cardiopulmonary bypass
TLDR
NAC appears to act as an oxygen free radical scavenger during open-heart surgery by reducing the oxidative burst response of neutrophils in the patients receiving NAC.
Hypoxic ventilatory drive in normal man.
TLDR
The data suggest, but do not prove, that oxygen tension in chemoreceptor tissue as in part determined by circulatory oxygen delivery may be an important factor in controlling the ventilatory response to hypoxia, as a continuous curve relating alveolar oxygen tension and minute ventilation.
...
...