Respiratory plasticity following intermittent hypoxia: roles of protein phosphatases and reactive oxygen species

2007 ◽  
Vol 35 (5) ◽  
pp. 1269-1272 ◽  
Author(s):  
J.E.R. Wilkerson ◽  
P.M. MacFarlane ◽  
M.S. Hoffman ◽  
G.S. Mitchell
Keyword(s):  
Reactive Oxygen Species ◽  
Motor Neurons ◽  
Intermittent Hypoxia ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Obstructive Sleep ◽  
Cord Injury ◽  
Respiratory Plasticity ◽  
Sustained Hypoxia ◽  
Synaptic Mechanisms

Plasticity is an important property of the respiratory control system. One of the best-studied models of respiratory plasticity is pLTF (phrenic long-term facilitation). pLTF is a progressive increase in phrenic motor output lasting several hours following acute exposure to intermittent hypoxia. Similar to many other forms of neuroplasticity, pLTF is pattern-sensitive; it is induced by intermittent, but not sustained hypoxia of similar cumulative duration. Our understanding of the cellular/synaptic mechanisms underlying pLTF has increased considerably in recent years. Here, we review accumulating evidence suggesting that the pattern-sensitivity of pLTF arises substantially from differential reactive oxygen species formation and subsequent protein phosphatase inhibition during intermittent compared with sustained hypoxia in or near phrenic motor neurons. A detailed understanding of the cellular/synaptic mechanisms of pLTF may provide the rationale for new pharmacological approaches in the treatment of severe ventilatory control disorders, such as obstructive sleep apnoea and respiratory insufficiency either following spinal cord injury or during neurodegenerative diseases such as amyotrophic lateral sclerosis.

scholarly journals Reactive oxygen species and respiratory plasticity following intermittent hypoxia

2008 ◽  
Vol 164 (1-2) ◽  
pp. 263-271 ◽  
Author(s):  
P.M. MacFarlane ◽  
J.E.R. Wilkerson ◽  
M.R. Lovett-Barr ◽  
G.S. Mitchell
Keyword(s):  
Reactive Oxygen Species ◽  
Intermittent Hypoxia ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Respiratory Plasticity

Hypersensitivity of lung vagal C fibers induced by acute intermittent hypoxia in rats: role of reactive oxygen species and TRPA1

2012 ◽  
Vol 303 (11) ◽  
pp. R1175-R1185 ◽  
Author(s):  
Mei-Ya Shen ◽  
Ya-Ling Luo ◽  
Chung-Huan Yang ◽  
Ting Ruan ◽  
Ching Jung Lai
Keyword(s):  
Reactive Oxygen Species ◽  
Intermittent Hypoxia ◽  
Transient Receptor Potential ◽  
Electrophysiological Study ◽  
Reactive Oxygen ◽  
Vagal Afferents ◽  
Radical Scavenger ◽  
Oxygen Species ◽  
C Fibers ◽  
Obstructive Sleep

Obstructive sleep apnea, manifested by intermittent hypoxia and excess production of reactive oxygen species (ROS) in airways, is associated with hyperreactive airway diseases, but the mechanism remains unclear. Sensitization of lung vagal C fibers (LVCFs) contributes to the airway hypersensitivity. We investigated the mechanisms underlying the sensitization of LVCFs with acute intermittent hypoxia (AIH), by 10 episodes of exposure to 30 s of hypoxic air (0%, 5%, or 10% O2) followed by 30 s of room air in anesthetized, open-chest, and artificially ventilated rats. Reflex apneic response to intravenous capsaicin (an LVCF stimulant), as measured by phrenic nerve activity, was concentration dependently augmented by AIH. Similarly, reflex apneic response to intravenous α,β-methylene-ATP (another LVCF stimulant) was augmented by AIH (0% O2). The reflex apnea evoked by these two stimulants was abolished by bilateral vagotomy, which suggests the involvement of lung vagal afferents. The AIH-augmented apneic response to these two stimulants was prevented by pretreatment with dimethylthiourea (a hydroxyl radical scavenger), N-acetyl-l-cysteine (an antioxidant) and HC-030031 [a transient receptor potential ankyrin 1 (TRPA1) receptor antagonist]. Consistently, electrophysiological study revealed the afferent responses of LVCFs to capsaicin or α,β-methylene-ATP were augmented by AIH, and this sensitization of LVCFs was prevented by dimethylthiourea, N-acetyl-l-cysteine, and HC-030031. In contrast, AIH did not alter the afferent response of LVCFs to mechanical stimulation by lung hyperinflation. We concluded that AIH sensitizes LVCFs in rats, thus resulting in exaggerated airway reflexogenic responses to chemical stimulants, possibly by ROS action and activation of TRPA1 receptors.

scholarly journals MKRN1 Ubiquitylates p21 to Protect against Intermittent Hypoxia-Induced Myocardial Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xue Bai ◽  
Hui Yang ◽  
Jiayuan Pu ◽  
Yan Zhao ◽  
Ying Jin ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Western Blot ◽  
Cell Apoptosis ◽  
Intermittent Hypoxia ◽  
Sleep Apnea Syndrome ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Myocardial Apoptosis ◽  
Protein Ubiquitination ◽  
Obstructive Sleep

Although chronic intermittent hypoxia- (IH-) induced myocardial apoptosis is an established pathophysiological process resulting in a poor prognosis for patients with obstructive sleep apnea syndrome, its underlying mechanism remains unclear. This study is aimed at exploring the role of makorin ring finger protein 1 (MKRN1) in IH-induced myocardial apoptosis and elucidating its molecular activity. First, the GSE2271 dataset was downloaded from the Gene Expression Omnibus database to identify the differentially expressed genes. Then, an SD rat model of IH, together with rat cardiomyocyte H9C2 and human cardiomyocyte AC16 IH models, was constructed. TUNEL, Western blot, and immunohistochemistry assays were used to detect cell apoptosis. Dihydroethidium staining was conducted to analyze the concentration of reactive oxygen species. In addition, RT-qPCR, Western blot, and immunohistochemistry were performed to measure the expression levels of MKRN1 and p21. The direct interaction between MKRN1 and p21 was determined using coimmunoprecipitation and ubiquitination analysis. MKRN1 expression was found to be downregulated in IH rat myocardial tissues as well as in H9C2 and AC16 cells. Upregulated expression of MKRN1 in H9C2 and AC16 cells alleviated the IH-induced reactive oxygen species production and cell apoptosis. Mechanistically, MKRN1 promoted p21 protein ubiquitination and the proteasome pathway degradation to negatively regulate p21 expression. Thus, MKRN1 regulates p21 ubiquitination to prevent IH-induced myocardial apoptosis.

Evidence that infiltrating neutrophils do not release reactive oxygen species in the site of spinal cord injury

2004 ◽  
Vol 190 (2) ◽  
pp. 414-424 ◽  
Author(s):  
R. de Castro ◽  
M.G. Hughes ◽  
G.-Y. Xu ◽  
C. Clifton ◽  
N.Y. Calingasan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cord Injury

scholarly journals Endothelin-1 mediates attenuated carotid baroreceptor activity by intermittent hypoxia

2012 ◽  
Vol 112 (1) ◽  
pp. 187-196 ◽  
Author(s):  
Ying-Jie Peng ◽  
Jayasri Nanduri ◽  
Xin Zhang ◽  
Ning Wang ◽  
Gayatri Raghuraman ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Intermittent Hypoxia ◽  
Carotid Sinus ◽  
Reactive Oxygen ◽  
Male Rats ◽  
Oxygen Species ◽  
Arterial Baroreflex ◽  
Endothelin 1 ◽  
Carotid Baroreceptor ◽  
Baroreflex Function

The objectives of the present study were to examine the effects of intermittent hypoxia (IH) on arterial baroreflex function and assess the underlying mechanism(s). Experiments were performed on adult male rats treated with 14 days of IH (15 s of hypoxia, 5 min of normoxia; 8 h/day) or normoxia (control). Arterial blood pressures were elevated in IH-treated rats, and this effect was associated with attenuated heart rate and splanchnic sympathetic nerve responses to arterial baroreflex activation. In IH-treated rats, carotid baroreceptor responses to elevated sinus pressures were attenuated. Endothelin-1 (ET-1) levels were elevated in the carotid sinus region of IH-treated rats, and this effect was associated with increased endothelin converting enzyme (ECE) activity, which generates biologically active ET-1. ETA receptor antagonist prevented the effects of IH on carotid baroreceptor activity. In IH-treated rats, reactive oxygen species (ROS) levels were elevated in the carotid sinus region, and antioxidant treatment prevented the effects of IH on ET-1 levels, ECE activity, carotid baroreceptor activity, and baroreflex function. These results demonstrate that 1) IH attenuates arterial baroreflex function, which is in part due to reduced carotid baroreceptor responses to elevated carotid sinus pressure, and 2) IH-induced carotid baroreceptor dysfunction involves reactive oxygen species-dependent upregulation of ET-1 signaling in the carotid sinus region.

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