<i>Ex vivo</i>exposure to carbon monoxide prevents hepatic ischemia/reperfusion injury through p38 MAP kinase pathway

Amersi, Farin; Shen, Xiu-Da; Anselmo, Dean M.; Melinek, Judy; Iyer, Suhasani; Southard, Daniel; Katori, Masamichi; Volk, Hans‐Dieter; Busuttil, Ronald W.; Buelow, Roland; Kupiec‐Weglinski, Jerzy W.

doi:10.1053/jhep.2002.32467

Cited by 219 publications

(150 citation statements)

References 40 publications

(63 reference statements)

Supporting

Mentioning

143

Contrasting

Unclassified

Order By: Relevance

“…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: 99%

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

Wang

Kim

et al. 2007

Journal of Biological Chemistry

171

146

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 99%

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

Wang

Kim

et al. 2007

Journal of Biological Chemistry

171

146

View full text Add to dashboard Cite

show abstract

“…The cytoprotective role of HO-1 has been observed recently in many kinds of cells including skeletal muscle (37), cardiomyocytes (38), hepatocytes (39,40), as well as in vascular endothelial cells (16,41). Several mechanisms could be responsible for the cytoprotective action of the HO-1.…”

Section: Discussionmentioning

confidence: 99%

ERK5 Activation Inhibits Inflammatory Responses via Peroxisome Proliferator-activated Receptor δ (PPARδ) Stimulation

Woo

Massett

Shishido

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptors (PPAR) decrease the production of cytokine and inducible nitric-oxide synthase (iNOS) expression, which are associated with aging-related inflammation and insulin resistance. Recently, the involvement of the induction of heme oxygenase-1 (HO-1) in regulating inflammation has been suggested, but the exact mechanisms for reducing inflammation by HO-1 remains unclear. We found that overexpression of HO-1 and [Ru(CO) 3 Cl 2 ] 2 , a carbon monoxide (CO)-releasing compound, increased not only ERK5 kinase activity, but also its transcriptional activity measured by luciferase assay with the transfection of the Gal4-ERK5 reporter gene. This transcriptional activity is required for coactivation of PPAR␦ by ERK5 in C2C12 cells. [Ru(CO) 3 Cl 2 ] 2 activated PPAR␦ transcriptional activity via the MEK5/ERK5 signaling pathway. The inhibition of NF-B activity by ERK5 activation was reversed by a dominant negative form of PPAR␦ suggesting that ERK5/PPAR␦ activation is required for the anti-inflammatory effects of CO and HO-1. Based on these data, we propose a new mechanism by which CO and HO-1 mediate anti-inflammatory effects via activating ERK5/PPAR␦, and ERK5 mediates CO and HO-1-induced PPAR␦ activation via its interaction with PPAR␦.Muscle wasting is a major feature of the cachexia associated with diverse pathologies such as cancer, sepsis, diabetes, and aging (1). Several cytokines have been implicated in the pathogenesis of muscle wasting, most notably TNF-␣, 2 a pro-inflammatory cytokine that was originally called "cachectin" (1). In addition, aging-related chronic low grade inflammation by TNF-␣ plays an important role in insulin resistance (2). It has been proposed that chronic inflammation by TNF-␣-mediated NF-B activation and subsequent inducible nitric-oxide synthase (iNOS) induction relates to muscle wasting and insulin resistance as we will explain below. Cai et al. (3) have shown that activation of NF-B, through muscle-specific transgenic expression of activated IB kinase ␤ (MIKK), causes profound muscle wasting that resembles clinical cachexia. In contrast, no overt phenotype was seen upon muscle-specific inhibition of NF-B through expression of IB suppressor (MISR), and denervation and tumor-induced muscle loss were substantially reduced and survival rates improved by NF-B inhibition in MISR mice, which is consistent with a critical role for NF-B in the pathology of muscle wasting, especially in diabetes and during the process of aging (3). Recent studies suggest the involvement of iNOS in the pathogenesis of insulin resistance (4, 5). First, most inducers of insulin resistance, including obesity (6), free fatty acids (7), hyperglycemia (8, 9), TNF-␣, oxidative stress, and endotoxin, increase iNOS expression. Second, iNOS mediates the impaired insulin-stimulated glucose uptake by treatment with TNF-␣ and lipopolysaccharide in cultured muscle cells (10). iNOS expression is elevated in skeletal muscle of patients with type 2 diabetes (11, 12), and high fat diet-induced...

show abstract

“…According to other studies about the tissue protective role of CO, the most efficacious concentration of CO ranges from Ϸ250 ppm to 1000 ppm. [12][13][14]16,17 The most beneficial concentration of CO may be specific for each species and each tissue. We cannot extrapolate the most efficacious condition of CO administration for the treatment of myocardial infarction in human beings from our data alone.…”

Section: Discussionmentioning

confidence: 99%

Carbon Monoxide Protects Against Cardiac Ischemia—Reperfusion Injury In Vivo via MAPK and Akt—eNOS Pathways

Fujimoto

Ohno

Ayabe

et al. 2004

ATVB

138

120

View full text Add to dashboard Cite

Background-Carbon monoxide (CO) is postulated to protect tissues against several types of injuries. We investigated the role of CO in amelioration of cardiac ischemia-reperfusion injury in vivo and the mechanisms involved in it. Methods and Results-Rats inhaled CO (250 ppm, 500 ppm, or 1000 ppm) for 24 hours in a chamber after myocardial ischemia-reperfusion induced by occluding the left anterior descending coronary artery for 30 minutes. Pre-exposure to 1000 ppm of CO significantly reduced the ratio of infarct areas to risk areas and suppressed the migration of macrophages and monocytes into infarct areas, and the expression of tumor necrosis factor (TNF)-␣ in the heart; however, 250 ppm, 500 ppm of CO, or low barometric pressure hypoxia (0.5 atm) did not affect them. Exposure to 1000 ppm CO resulted in the activation of p38 mitogen-activated protein kinase (p38MAPK), protein kinase B␣(Akt), endothelial nitric oxide synthase (eNOS), and cyclic guanosine monophosphate (cGMP) in the myocardium. Inhibition of p38MAPK, PI3kinase, NO, and soluble guanylate cyclase with SB203580, wortmannin, N(G)-nitro-L-arginine methyl ester (L-NAME), and methylene blue, respectively, attenuated the cytoprotection by CO. Conclusion-CO has beneficial effects on cardiac ischemia-reperfusion injury; this effect is mediated by p38MAPK pathway and Akt-eNOS pathway, including production of cGMP.

show abstract

Ex vivoexposure to carbon monoxide prevents hepatic ischemia/reperfusion injury through p38 MAP kinase pathway

Cited by 219 publications

References 40 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

ERK5 Activation Inhibits Inflammatory Responses via Peroxisome Proliferator-activated Receptor δ (PPARδ) Stimulation

Carbon Monoxide Protects Against Cardiac Ischemia—Reperfusion Injury In Vivo via MAPK and Akt—eNOS Pathways

Contact Info

Product

Resources

About