scholarly journals HIF-1α-Mediated, NADPH Oxidase-Derived ROS Contributes to Laryngeal Airway Hyperreactivity Induced by Intermittent Hypoxia in Rats

2020 ◽  
Vol 11 ◽  
Author(s):  
You Shuei Lin ◽  
Yan-Jhih Shen ◽  
Ping-Hsun Ou ◽  
Ching Jung Lai
2009 ◽  
Vol 29 (15) ◽  
pp. 4903-4910 ◽  
Author(s):  
Y.- J. Peng ◽  
J. Nanduri ◽  
G. Yuan ◽  
N. Wang ◽  
E. Deneris ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Larissa Dyugovskaya ◽  
Slava Berger ◽  
Andrey Polyakov ◽  
Peretz Lavie ◽  
Lena Lavie

Previously we identified, for the first time, a new small-size subset of neutrophil-derived giant phagocytes (Gϕ) which spontaneously developin vitrowithout additional growth factors or cytokines. Gϕare CD66b+/CD63+/MPO+/LC3B+and are characterized by extended lifespan, large phagolysosomes, active phagocytosis, and reactive oxygen species (ROS) production, and autophagy largely controls their formation. Hypoxia, and particularly hypoxia/reoxygenation, is a prominent feature of many pathological processes. Herein we investigated Gϕformation by applying various hypoxic conditions. Chronic intermittent hypoxia (IH) (29 cycles/day for 5 days) completely abolished Gϕformation, while acute IH had dose-dependent effects. Exposure to 24 h (56 IH cycles) decreased their size, yield, phagocytic ability, autophagy, mitophagy, and gp91-phox/p22-phoxexpression, whereas under 24 h sustained hypoxia (SH) the size and expression of LC3B and gp91-phox/p22-phoxresembled Gϕformed in normoxia. Diphenyl iodide (DPI), a NADPH oxidase inhibitor, as well as the PI3K/Akt and autophagy inhibitor LY294002 abolished Gϕformation at all oxygen conditions. However, the potent antioxidant, N-acetylcysteine (NAC) abrogated the effects of IH by inducing large CD66b+/LC3B+Gϕand increased both NADPH oxidase expression and phagocytosis. These findings suggest that NADPH oxidase, autophagy, and the PI3K/Akt pathway are involved in Gϕdevelopment.


2021 ◽  
Vol 125 (4) ◽  
pp. 1146-1156
Author(s):  
Nicole L. Nichols ◽  
Gordon S. Mitchell

Distinct mechanisms give rise to pLTF induced by moderate and severe AIH. We demonstrate that, unlike moderate AIH, severe AIH-induced pLTF requires EPAC and PI3K/Akt and is marginally constrained by NADPH oxidase activity. Surprisingly, sAIH-induced pLTF requires MEK/ERK activity similar to moderate AIH-induced pLTF and is reduced by PKA inhibition. We suggest sAIH-induced pLTF arises from complex interactions between dominant mechanisms characteristic of moderate versus severe AIH-induced pLTF.


2009 ◽  
Vol 106 (5) ◽  
pp. 1584-1592 ◽  
Author(s):  
Tung-Lung Tsai ◽  
Shyue-Yih Chang ◽  
Ching-Yin Ho ◽  
Yu Ru Kou

The pathogenetic mechanisms of laryngeal airway hyperreactivity (LAH) in patients with extraesophageal reflux are unclear. We recently reported that a laryngeal acid-pepsin insult produces LAH that is mediated through sensitization of the capsaicin-sensitive laryngeal afferent fibers by reactive oxygen species (ROS) in rats. Since ROS may promote the release of ATP from cells, we hypothesized that activation of P2X purinoceptors by ATP subsequent to an increase in ROS induces LAH in an inflamed larynx that has been insulted by acid-pepsin or H2O2 (a major type of ROS). The larynxes of 208 anesthetized rats were functionally isolated while the animals breathed spontaneously. Ammonia vapor was delivered into the larynx to measure laryngeal reflex reactivity. Laryngeal insult with acid-pepsin or H2O2 produced LAH with similar characteristics. The H2O2-induced LAH was prevented by laryngeal pretreatment with dimethylthiourea (a hydroxyl radical scavenger), suggesting a critical role for ROS. The LAH induced by both insults were completely prevented by ATP scavengers (a combination of apyrase and adenosine deaminase) or a P2X receptor antagonist ( iso-pyridoxalphosphate-6-azophenyl-2′,5′-disulfonate). Laryngeal application of a P2X receptor agonist (α,β-methylene-ATP) also produced LAH. An insult with either acid-pepsin or H2O2 similarly promoted an increase in the levels of ATP, lipid peroxidation, and inflammation in the larynx. Our findings suggest that laryngeal insult with acid-pepsin or H2O2 induces inflammation and produces excess ROS in the rat's larynx. The latter may in turn promote the release of ATP to activate P2X receptors, resulting in sensitization of capsaicin-sensitive laryngeal afferent fibers and LAH.


2008 ◽  
Vol 294 (5) ◽  
pp. H2197-H2203 ◽  
Author(s):  
Tetsuya Hayashi ◽  
Chika Yamashita ◽  
Chika Matsumoto ◽  
Chol-Jun Kwak ◽  
Kiwako Fujii ◽  
...  

Intermittent hypoxia due to sleep apnea syndrome is associated with cardiovascular diseases. However, the precise mechanisms by which intermittent hypoxic stress accelerates cardiovascular diseases are largely unclear. The aim of this study was to investigate the role of gp91 phox-containing NADPH oxidase in the development of left ventricular (LV) remodeling induced by intermittent hypoxic stress in mice. Male gp91 phox-deficient (gp91−/−) mice ( n = 26) and wild-type ( n = 39) mice at 7–12 wk of age were exposed to intermittent hypoxia (30 s of 4.5–5.5% O2 followed by 30 s of 21% O2 for 8 h/day during daytime) or normoxia for 10 days. Mean blood pressure and LV systolic and diastolic function were not changed by intermittent hypoxia in wild-type or gp91−/− mice, although right ventricular systolic pressure tended to be increased. In wild-type mice, intermittent hypoxic stress significantly increased the diameter of cardiomyocytes and interstitial fibrosis in LV myocardium. Furthermore, intermittent hypoxic stress increased superoxide production, 4-hydroxy-2-nonenal protein, TNF-α and transforming growth factor-β mRNA, and NF-κB binding activity in wild-type, but not gp91−/−, mice. These results suggest that gp91 phox-containing NADPH oxidase plays a crucial role in the pathophysiology of intermittent hypoxia-induced LV remodeling through an increase of oxidative stress.


2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Jayasri Nanduri ◽  
Damodara Vaddi ◽  
Shakil Khan ◽  
Ning Wang ◽  
Vladislav Makarenko ◽  
...  

2015 ◽  
Vol 6 ◽  
Author(s):  
Robert Williams ◽  
Paul Lemaire ◽  
Philip Lewis ◽  
Fiona B. McDonald ◽  
Eric Lucking ◽  
...  

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