Carbon Monoxide Inhibition of Apoptosis during Ischemia-Reperfusion Lung Injury Is Dependent on the p38 Mitogen-activated Protein Kinase Pathway and Involves Caspase 3

Zhang, Xuchen; Shan, Peiying; Otterbein, Leo E.; Alam, Jawed; Flavell, Richard A.; Davis, Roger J.; Choi, Augustine M.K.; Lee, Patricia

doi:10.1074/jbc.m208419200

Cited by 249 publications

(203 citation statements)

References 66 publications

(65 reference statements)

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“…In rodent models of hyperoxia-induced lung injury, CO exerts potent anti-inflammatory effects with reduced inflammatory cell influx into the lungs and marked attenuation in the expression of pro-inflammatory cytokines (17). CO suppressed arteriosclerotic lesion formation associated with chronic graft rejection and with balloon injury (27) and inhibited apoptosis during ischemia-reperfusion injury (26,48,49). These effects were associated with the CO-dependent activation of the p38 mitogen-activated protein kinase pathway.…”

Section: Discussionmentioning

confidence: 95%

Carbon Monoxide Protects against Hyperoxia-induced Endothelial Cell Apoptosis by Inhibiting Reactive Oxygen Species Formation

Wang

Kim

et al. 2007

Journal of Biological Chemistry

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171

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Hyperoxia causes cell injury and death associated with reactive oxygen species formation and inflammatory responses. Recent studies show that hyperoxia-induced cell death involves apoptosis, necrosis, or mixed phenotypes depending on cell type, although the underlying mechanisms remain unclear. Using murine lung endothelial cells, we found that hyperoxia caused cell death by apoptosis involving both extrinsic (Fasdependent) and intrinsic (mitochondria-dependent) pathways. Hyperoxia-dependent activation of the extrinsic apoptosis pathway and formation of the death-inducing signaling complex required NADPH oxidase-dependent reactive oxygen species production, because this process was attenuated by chemical inhibition, as well as by genetic deletion of the p47 phox subunit, of the oxidase. Overexpression of heme oxygenase-1 prevented hyperoxia-induced cell death and cytochrome c release. Likewise, carbon monoxide, at low concentrations, markedly inhibited hyperoxiainduced endothelial cell death by inhibiting cytochrome c release and caspase-9/3 activation. Carbon monoxide, by attenuating hyperoxia-induced reactive oxygen species production, inhibited extrinsic apoptosis signaling initiated by death-inducing signal complex trafficking from the Golgi apparatus to the plasma membrane and downstream activation of caspase-8. We also found that carbon monoxide inhibited the hyperoxia-induced activation of Bcl-2-related proteins involved in both intrinsic and extrinsic apoptotic signaling. Carbon monoxide inhibited the activation of Bid and the expression and mitochondrial translocation of Bax, whereas promoted Bcl-X L /Bax interaction and increased Bad phosphorylation. We also show that carbon monoxide promoted an interaction of heme oxygenase-1 with Bax. These results define novel mechanisms underlying the antiapoptotic effects of carbon monoxide during hyperoxic stress.The clinical treatment of respiratory failure often requires supplemental oxygen therapy. Prolonged exposure to an elevated oxygen tension (hyperoxia) in animal models causes acute and chronic lung injury that resembles acute respiratory distress syndrome. In rodent models, hyperoxia triggers an extensive inflammatory response in the lung that degrades the alveolar-capillary barrier, leading to impaired gas exchange and pulmonary edema (1, 2). Lung tissue damage results from the direct action of increased intracellular reactive oxygen species (ROS) 2 or as a secondary consequence of inflammatory responses of the host (3, 4). The source(s) of intracellular ROS during oxygen exposure remain unclear but may involve increased mitochondrial generation and/or activation of NADPH oxidases (5, 6). The pathological changes in hyperoxiainjured lungs coincide with the injury or death of pulmonary capillary endothelial cells and alveolar epithelial cells (2, 4 -7). Epithelial cells maintain the integrity of the alveolar-capillary barrier and defend against oxidative injury. Compromised epithelial cell function may permit fluid and macromolecules to leak into the air...

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Section: Discussionmentioning

confidence: 95%

Carbon Monoxide Protects against Hyperoxia-induced Endothelial Cell Apoptosis by Inhibiting Reactive Oxygen Species Formation

Wang

Kim

et al. 2007

Journal of Biological Chemistry

Self Cite

171

146

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“…Some reports have demonstrated the potent antioxidative and cytoprotective properties of hemederived metabolites generated by HO-1 against various stress stimuli [26]. Microsomal epoxide hydrolase (EHm), which is another phase II enzyme and catalyzes the addition of H 2 O across the epoxide to form the corresponding diol [15], was also up-regulated by Dox and SFE treatment.…”

Section: Discussionmentioning

confidence: 99%

Schisandra fructus extract ameliorates doxorubicin-induce cytotoxicity in cardiomyocytes: altered gene expression for detoxification enzymes

et al. 2007

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The effect of Schisandra fructus extract (SFE) on doxorubicin (Dox)-induced cardiotoxicity was investigated in H9c2 cardiomyocytes. Dox, which is an antineoplastic drug known to induce cardiomyopathy possibly through production of reactive oxygen species, induced significant cytotoxicity, intracellular reactive oxygen species (ROS), and lipid peroxidation. SFE treatment significantly increased cell survival up to 25%, inhibited intracellular ROS production in a time-and dosedependent manner, and inhibited lipid peroxidation induced by Dox. In addition, SFE treatment induced expression of cellular glutathione S-transferases (GSTs), which function in the detoxification of xenobiotics, and endogenous toxicants including lipid peoxides. Analyses of 31,100 genes using Affymetrix cDNA microarrays showed that SFE treatment up-regulated expression of genes involved in glutathione metabolism and detoxification [GST theta 1, mu 1, and alpha type 2, heme oxygenase 1 (HO-1), and microsomal epoxide hydrolase (mEH)] and energy metabolism [carnitine palmitoyltransferase-1 (CPT-1), transaldolase, and transketolase]. These data indicated that SFE might increase the resistance to cardiac cell injury by Dox, at least partly, together with altering gene expression, especially induction of phase II detoxification enzymes.

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“…Recent evidence suggests that pathways independent of cGMP are important in mediating CO signaling pathways. These cGMP-independent pathways include the ERK MAPK in airway smooth muscle cell proliferation (33), p38-␣ MAPK and Egr-1 pathways in ischemia-reperfusion lung injury (34,35), AP-1 in murine macrophages in response to LPS, and the p21 and p38 MAPK pathway in vascular smooth muscle cell proliferation (19,36). We showed that NF-B and AP-1 activation, two major pathways in VILI (7,10), are not modulated by CO inhalation in VILI.…”

Section: Discussionmentioning

confidence: 99%

Inhaled Carbon Monoxide Confers Antiinflammatory Effects against Ventilator-induced Lung Injury

Dolinay

Szilasi

Liu

et al. 2004

Am J Respir Crit Care Med

138

127

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Ventilator-induced lung injury (VILI) is a major cause of morbidity and mortality in intensive care units. The stress-inducible gene product, heme oxygenase-1, and carbon monoxide (CO), a major byproduct of heme oxygenase catalysis of heme, have been shown to confer potent antiinflammatory effects in models of tissue and cellular injury. In this study, we observed increased expression of heme oxygenase-1 mRNA and protein in a rat model of VILI. To assess the physiologic function of heme oxygenase-1 induction in VILI, we determined whether low concentration of inhaled CO could serve to protect the lung against VILI. Low concentration of inhaled CO significantly reduced tumor necrosis factor-␣ levels and total cell count in lavage fluid, while simultaneously elevating levels of antiinflammatory interleukin-10 levels. To better characterize the mechanism of CO-mediated antiinflammatory effects, we examined key signaling pathways, which may mediate CO-induced antiinflammatory effects. We demonstrate that inhaled CO exerts antiinflammatory effects in VILI via the p38 mitogen-activated protein kinase pathway but independent of activator protein-1 and nuclear factor-B pathways. Our data lead to a tempting speculation that inhaled CO might be useful in minimizing VILI. Keywords: cytokines; heme oxygenase-1; p38 MAPKAccording to an international study, an average of 39% of intensive care unit patients requires mechanical ventilation worldwide (1). Many of these patients develop ventilator-induced lung injury (VILI) (2). Eventually VILI contributes to acute respiratory distress syndrome (ARDS), which has a 40 to 50% mortality rate (3). Although clinical trials showed that ARDS/VILI-related mortality could be attenuated with lower tidal volume ventilation, positive end-expiratory pressure (PEEP) ventilation, and more recently, with recruitment maneuver combined with protective ventilation strategy, the syndrome remains a major problem in intensive care units (3)(4)(5).It is established that mechanical ventilators that apply high volumes and pressures can lead to increased alveolar-capillary permeability (6). This loss of compartmentalization results in increased fluid influx to the alveoli from the capillaries, causing pulmonary edema. The injured or ruptured cells attract neutrophil leukocytes and activate alveolar macrophages, causing inflammation in the lung (6). Tremblay and colleagues have suggested that ventilation can provoke an inflammatory response in the distal airway and alveolar cells (7), manifested by increased production of proinflammatory cytokines. It is speculated that the released proinflammatory cytokines could enter the circulation causing inflammation in other systemic organs. In addition, the previously diseased or injured lungs are more susceptible to subsequent mechanical ventilation, releasing more proinflammatory cytokines than healthy lungs, perhaps reflecting the cumulative effects of multiple injuries (8, 9). Lipopolysaccharide (LPS), acid aspiration, and cecal ligation/perforation-induced sep...

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Carbon Monoxide Inhibition of Apoptosis during Ischemia-Reperfusion Lung Injury Is Dependent on the p38 Mitogen-activated Protein Kinase Pathway and Involves Caspase 3

Cited by 249 publications

References 66 publications

Carbon Monoxide Protects against Hyperoxia-induced Endothelial Cell Apoptosis by Inhibiting Reactive Oxygen Species Formation

Carbon Monoxide Protects against Hyperoxia-induced Endothelial Cell Apoptosis by Inhibiting Reactive Oxygen Species Formation

Schisandra fructus extract ameliorates doxorubicin-induce cytotoxicity in cardiomyocytes: altered gene expression for detoxification enzymes

Inhaled Carbon Monoxide Confers Antiinflammatory Effects against Ventilator-induced Lung Injury

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