Mechanical stress activates xanthine oxidoreductase through MAP kinase-dependent pathways

Abdulnour, Raja Elie E.; Peng, Xiaoping; Finigan, James H.; Han, Eugenia J.; Hasan, Emile; Birukov, Konstantin G.; Reddy, Sekhar P.; Watkins, James E.; Kayyali, Usamah S.; Garcia, Joe G.N.; Tuder, Rubin M.; Hassoun, Paul M.

doi:10.1152/ajplung.00453.2005

Cited by 89 publications

(83 citation statements)

References 36 publications

(40 reference statements)

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“…[30][31][32] However, it is still unclear that HCA attenuated the oxidative stress and inflammatory injury induced by the lung mechanical stretch, inhibited the activation of ASK1/JNK and p38 MAP kinase, which have the ability to mediate apoptosis, and contributed to increase capillary permeability. This study demonstrates that high-pressure mechanical ventilation in the rat for 4 h caused lung oxidative stress and inflammatory injury, lung edema formation, and apoptosis, which were attenuated by HCA (PaCO 2 at 80-100 mm Hg) and accompanied by a decrease in the activity of ASK1/JNK and p38 MAP kinase.…”

Section: Discussionmentioning

confidence: 99%

Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury

Yang

Song

Wang

et al. 2013

Laboratory Investigation

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Hypercapnic acidosis may attenuate ventilator-induced lung oxidative stress injury and alveolar cell apoptosis, but the underlying mechanisms are poorly understood. We examined the effects of hypercapnic acidosis on the role of apoptosis signal-regulating kinase 1 (ASK1), which activates the c-Jun N-terminal kinase (JNK) and p38 cascade in both apoptosis and oxidative reactions, in high-pressure ventilation stimulated rat lungs. Rats were ventilated with a peak inspiratory pressure (PIP) of 30 cmH 2 O for 4 h and randomly given FiCO 2 to achieve normocapnia (PaCO 2 at 35-45 mm Hg) or hypercapnia (PaCO 2 at 80-100 mm Hg); normally ventilated rats with PIP of 15 cmH 2 O were used as controls. Lung injury was quantified by gas exchange, microvascular leaks, histology, levels of inflammatory cytokines, and pulmonary oxidative reactions. Apoptosis through the ASK1-JNK/p38 mitogen-activated protein kinase (MAPK) cascade in type II alveolar epithelial cells (AECIIs) were evaluated by examination of caspase-3 activation. The results showed that injurious ventilation caused significant lung injury, including deteriorative oxygenation, changes of histology, and the release of inflammatory cytokines. In addition, the high-pressure mechanical stretch also induced apoptosis and caspase-3 activation in the AECIIs. Hypercapnia attenuated these responses, suppressing the ASK1 signal pathways with its downstream kinase phosphorylation of p38 MAPK and JNK, and caspase-3 activation. Thus, hypercapnia can attenuate cell apoptosis and oxidative stress damage in rat lungs during injurious ventilation, at least in part, due to the suppression of the ASK1-JNK/p38 MAPK pathways.

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Section: Discussionmentioning

confidence: 99%

Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury

Yang

Song

Wang

et al. 2013

Laboratory Investigation

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“…We assessed lung vascular permeability using the Evans blue dye technique as previously described (30)(31)(32). Exposure to MV at LVT caused no significant increase in extravasation of Evans blue in both genotypes compared with the respective SpV control groups (results not shown).…”

Section: Disruption Of Nrf2 Augments Mv-induced Lung Vascular Leak Anmentioning

confidence: 99%

“…Exposure to MV was performed as previously described (30)(31)(32). Briefly, 6-to 8-week-old male mice (25-30 g) were used for these studies unless otherwise indicated.…”

Section: MVmentioning

confidence: 99%

“…The adequacy of MV settings on gas exchange was confirmed in preliminary experiments in which arterial blood gases obtained via catheterization of a femoral artery were analyzed by an automated blood gas analyzer (model 348 Blood Gas Analyzer; Chiron Diagnostics; Norwood, MA) as previously described (31,32). Arterial blood gas analysis revealed stable levels of arterial oxygen (Pa O 2 of 55-90 mm Hg) and carbon dioxide (Pa CO 2 of 30-50 mm Hg) ( Table 1).…”

Section: MVmentioning

confidence: 99%

“…BALF protein concentration was measured by BCA Protein Assay kit (Pierce Chemical Co., Rockford, IL). Lung vascular permeability was determined using Evans blue injections as previously detailed (30)(31)(32). Extravasated Evans blue concentration in lung homogenates was calculated against a standard curve and expressed as micrograms of Evans blue per milligram of lung tissue as previously described (30)(31)(32).…”

Section: Assessment Of Lung Injury and Inflammation In Bronchoalveolamentioning

confidence: 99%

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Genetic and Pharmacologic Evidence Links Oxidative Stress to Ventilator-induced Lung Injury in Mice

Papaiahgari

Yerrapureddy

Reddy

et al. 2007

Am J Respir Crit Care Med

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Rationale: Mechanical ventilation (MV) is an indispensable therapy for critically ill patients with acute lung injury and the adult respiratory distress syndrome. However, the mechanisms by which conventional MV induces lung injury remain unclear. Objectives: We hypothesized that disruption of the gene encoding Nrf2, a transcription factor that regulates the induction of several antioxidant enzymes, enhances susceptibility to ventilator-induced lung injury (VILI) and that antioxidant supplementation attenuates this effect. Methods: To test our hypothesis and to examine the relevance of oxidative stress in VILI, we assessed lung injury and inflammatory responses in Nrf2-deficient (Nrf2 2/2 ) mice and wild-type (Nrf2 1/1 ) mice after an acute (2-h) injurious model of MV with or without administration of antioxidant. Measurements and Main Results: Nrf2 2/2 mice displayed greater levels of lung alveolar and vascular permeability and inflammatory responses to MV as compared with Nrf2 1/1 mice. Nrf2 deficiency enhances the levels of several proinflammatory cytokines implicated in the pathogenesis of VILI. We found diminished levels of critical antioxidant enzymes and redox imbalance by MV in the lungs of Nrf2 2/2 mice; however, antioxidant supplementation to Nrf2 2/2 mice remarkably attenuated VILI. When subjected to a clinically relevant prolong period of MV, Nrf2 2/2 mice displayed greater levels of VILI than Nrf2 1/1 mice. Expression profiling revealed lack of induction of several VILI genes, stress response and solute carrier proteins, and phosphatases in Nrf2 2/2 mice. Conclusions: Our data demonstrate for the first time a critical role for Nrf2 in VILI, which confers protection against cellular responses induced by MV by modulating oxidative stress.

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Mechanosensing and Mechanoregulation of Endothelial Cell Functions

Fang

Birukov

2019

Comprehensive Physiology

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120

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Vascular endothelial cells (ECs) form a semiselective barrier for macromolecules and cell elements regulated by dynamic interactions between cytoskeletal elements and cell adhesion complexes. ECs also participate in many other vital processes including innate immune reactions, vascular repair, secretion, and metabolism of bioactive molecules. Moreover, vascular ECs represent a unique cell type exposed to continuous, time-dependent mechanical forces: different patterns of shear stress imposed by blood flow in macrovasculature and by rolling blood cells in the microvasculature; circumferential cyclic stretch experienced by the arterial vascular bed caused by heart propulsions; mechanical stretch of lung microvascular endothelium at different magnitudes due to spontaneous respiration or mechanical ventilation in critically ill patients. Accumulating evidence suggests that vascular ECs contain mechanosensory complexes, which rapidly react to changes in mechanical loading, process the signal, and develop context-specific adaptive responses to rebalance the cell homeostatic state. The significance of the interactions between specific mechanical forces in the EC microenvironment together with circulating bioactive molecules in the progression and resolution of vascular pathologies including vascular injury, atherosclerosis, pulmonary edema, and acute respiratory distress syndrome has been only recently recognized. This review will summarize the current understanding of EC mechanosensory mechanisms, modulation of EC responses to humoral factors by surrounding mechanical forces (particularly the cyclic stretch), and discuss recent findings of magnitude-specific regulation of EC functions by transcriptional, posttranscriptional and epigenetic mechanisms using-omics approaches. We also discuss ongoing challenges and future opportunities in developing new therapies targeting dysregulated mechanosensing mechanisms to treat vascular diseases.

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Mechanical stress activates xanthine oxidoreductase through MAP kinase-dependent pathways

Cited by 89 publications

References 36 publications

Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury

Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury

Genetic and Pharmacologic Evidence Links Oxidative Stress to Ventilator-induced Lung Injury in Mice

Mechanosensing and Mechanoregulation of Endothelial Cell Functions

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