Xanthine oxidase-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle

McCutchan, H. J.; Schwappach, John; Enquist, Erik; Walden, D. L.; Terada, Lance S.; Reiss, Oscar K.; Leff, Jonathan A.; Repine, John E.

doi:10.1152/ajpheart.1990.258.5.h1415

Cited by 34 publications

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“…The role of xanthine oxidase in I/R injury has been described extensively (3,24,27), and the discovery that the activity of this enzyme is elevated after contractile claudication is in agreement with our previous findings (21). However, the novel finding is that by administering allopurinol to attenuate the increase in xanthine oxidase activity, we were able to show attenuation of lipid peroxidation, muscle damage, and neutrophil infiltration.…”

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confidence: 91%

Xanthine oxidase and activated neutrophils cause oxidative damage to skeletal muscle after contractile claudication

Judge

Dodd

2004

American Journal of Physiology-Heart and Circulatory Physiology

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Judge, A. R., and S. L. Dodd. Xanthine oxidase and activated neutrophils cause oxidative damage to skeletal muscle after contractile claudication. Am J Physiol Heart Circ Physiol 286: H252-H256, 2004. First published September 11, 2003 10.1152/ajpheart.00684. 2003.-We previously showed oxidative damage and edema within skeletal muscle after contractile claudication. To investigate the sources of this oxidative damage in the gastrocnemius muscle, we administered allopurinol (Allo, to inhibit xanthine oxidase) and cyclophosphamide (Cyclo, to deplete neutrophils) before inducing contractile claudication in male Sprague Dawley rats. Contractile claudication (ligated stimulated, LS) caused a significant increase in xanthine oxidase activity [sham ligated stimulated (SS) ϭ 2.57 Ϯ 0.07; LS ϭ 3.22 Ϯ 0.07] and neutrophil infiltration (SS ϭ 0.47 Ϯ 0.03; LS ϭ 0.91 Ϯ 0.10) compared with controls (SS), and this was associated with increased lipid peroxidation, protein oxidation, muscle damage, and edema. Pretreatment with Allo attenuated the increase in xanthine oxidase activity and attenuated lipid hydroperoxides (control LS ϭ 12.85 Ϯ 0.50; Allo LS ϭ 9.96 Ϯ 0.71), muscle damage, and neutrophil infiltration (control LS ϭ 0.91 Ϯ 0.10; Allo LS ϭ 0.61 Ϯ 0.07). This latter finding suggests that xanthine oxidasederived oxidants are chemotactic to neutrophils. Pretreatment with Cyclo reduced neutrophil infiltration (control LS ϭ 0.91 Ϯ 0.10; Cyclo LS ϭ 0.55 Ϯ 0.02) and attenuated lipid peroxidation (control LS ϭ 12.85 Ϯ 0.50; Cyclo LS ϭ 6.462 Ϯ 0.62), protein oxidation (control LS ϭ 2.59 Ϯ 0.47; Cyclo LS ϭ 1.77 Ϯ 0.60), muscle damage, and edema. Together, these data indicate that contractile claudication causes an increase in xanthine oxidase activity and neutrophils in muscle and that inhibition of these oxidant sources protects against oxidative stress, muscle damage, and edema. occlusion; free radicals; reactive oxygen species; muscle contraction SEVERAL STUDIES HAVE SHOWN that ischemia-reperfusion (I/R) caused by exercise claudication elevates markers of oxidative damage in the plasma. Hickman et al. (16) exercised claudicant patients for 10 min and found an increase in plasma malondialdehyde levels after exercise, whereas Silvestro et al. (32) showed an increase in thiobarbituric acid-reactive substances, as a marker of lipid peroxidation, after maximal, but not submaximal, exercise in claudicants.Likewise, markers of oxidative damage are also elevated in skeletal muscle after claudication. We recently found (21) an increase in protein oxidation and lipid peroxidation and a reduction in total glutathione levels 1 h after exercise with an animal model of claudication. This was associated with an increase in xanthine oxidase activity and neutrophils-both sources of oxidizing species.To further explore these findings and determine the relative contributions of each pathway, we chose to 1) inhibit xanthine oxidase activity and 2) deplete neutrophils and then measure markers of oxidative damage. Thus the purpose of this study wa...

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Section: Discussionsupporting

confidence: 91%

Xanthine oxidase and activated neutrophils cause oxidative damage to skeletal muscle after contractile claudication

Judge

Dodd

2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…The mitochondrial electron transport system is considered the major intracellular source for the production of ROS (4, 5, 27, 36, 48, 50 -52). There are other potential sources in skeletal muscle, including cytosolic NAD(P)H oxidase (3,22), infiltrating phagocyte cells (24), and endothelial tissue containing xanthine oxidase (26,28). Nitric oxide (NO), one of the RNS, is also produced in contracting skeletal muscle by NO synthase (23,32).…”

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Possible involvement of the α1 isoform of 5′AMP-activated protein kinase in oxidative stress-stimulated glucose transport in skeletal muscle

Toyoda¹,

Hayashi²,

Miyamoto³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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182

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Possible involvement of the ␣1 isoform of 5ЈAMP-activated protein kinase in oxidative stressstimulated glucose transport in skeletal muscle. Am J Physiol Endocrinol Metab 287: E166 -E173, 2004. First published March 16, 2004 10.1152/ajpendo.00487.2003.-Recent studies have suggested that 5ЈAMP-activated protein kinase (AMPK) is activated in response to metabolic stresses, such as contraction, hypoxia, and the inhibition of oxidative phosphorylation, which leads to insulin-independent glucose transport in skeletal muscle. In the present study, we hypothesized that acute oxidative stress increases the rate of glucose transport via an AMPK-mediated mechanism. When rat epitrochlearis muscles were isolated and incubated in vitro in Krebs buffer containing the oxidative agent H2O2, AMPK␣1 activity increased in a time-and dose-dependent manner, whereas AMPK␣2 activity remained unchanged. The activation of AMPK␣1 was associated with phosphorylation of AMPK Thr 172 , suggesting that an upstream kinase is involved in the activation process. H2O2-induced AMPK␣1 activation was blocked in the presence of the antioxidant N-acetyl-L-cysteine (NAC), and H 2O2 significantly increased the ratio of oxidized glutathione to glutathione (GSSG/GSH) concentrations, a sensitive marker of oxidative stress. H2O2 did not cause an increase in the conventional parameters of AMPK activation, such as AMP and AMP/ATP. H2O2 increased 3-O-methyl-D-glucose transport, and this increase was partially, but significantly, blocked in the presence of NAC. Results were similar when the muscles were incubated in a superoxide-generating system using hypoxanthine and xanthine oxidase. Taken together, our data suggest that acute oxidative stress activates AMPK␣1 in skeletal muscle via an AMP-independent mechanism and leads to an increase in the rate of glucose transport, at least in part, via an AMPK␣1-mediated mechanism.

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“…Ischemia/reperfusion produces oxidative stress through the irreversible conversion of xanthine dehydrogenase to xanthine oxidase (XO) during ischemia with consequent production of oxygen-free radicals and H 2 O 2 during reperfusion (4,5). Several lines of evidence suggest a role for oxidative stress as contributing to activation of hematopoietic cells.…”

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Oxidative Stress Reprograms Lipopolysaccharide Signaling via Src Kinase-dependent Pathway in RAW 264.7 Macrophage Cell Line

Khadaroo

Kapùs

Powers

et al. 2003

Journal of Biological Chemistry

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Oxidative stress generated during ischemia/reperfusion injury has been shown to augment cellular responsiveness. Whereas oxidants are themselves known to induce several intracellular signaling cascades, their effect on signaling pathways initiated by other inflammatory stimuli remains poorly elucidated. Previous work has suggested that oxidants are able to prime alveolar macrophages for increased NF-B translocation in response to treatment with lipopolysaccharide (LPS). Because oxidants are known to stimulate the Src family of tyrosine kinases, we hypothesized that the oxidants might contribute to augmented NF-B translocation by LPS via the involvement of Src family kinases. To model macrophage priming in vitro, the murine macrophage cell line, RAW 264.7, was first incubated with various oxidants and then exposed to low dose LPS. These studies show that oxidant stress is able to augment macrophage responsiveness to LPS as evidenced by earlier and increased NF-B translocation. Inhibition of the Src family kinases by either pharmacological inhibition using PP2 or through a molecular approach by cell transfection with Csk was found to prevent the augmented LPS-induced NF-B translocation caused by oxidants. Interestingly, while Src kinase inhibition was able to prevent the LPS-induced NF-B translocation in oxidant-treated macrophages, this strategy had no effect on NF-B translocation caused by LPS in the absence of oxidants. These findings suggested that oxidative stress might divert LPS signaling along an alternative signaling pathway. Further studies demonstrated that the Srcdependent pathway induced by oxidant pretreatment involved the activation of phosphatidylinositol 3-kinase. Involvement of this pathway appeared to be independent of traditional LPS signaling. Together, these studies provide a novel potential mechanism whereby oxidants might prime alveolar macrophages for altered responsiveness to subsequent inflammatory stimuli and suggest different cellular targets for immunomodulation following ischemia/reperfusion.

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Xanthine oxidase-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle

Cited by 34 publications

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Xanthine oxidase and activated neutrophils cause oxidative damage to skeletal muscle after contractile claudication

Xanthine oxidase and activated neutrophils cause oxidative damage to skeletal muscle after contractile claudication

Possible involvement of the α1 isoform of 5′AMP-activated protein kinase in oxidative stress-stimulated glucose transport in skeletal muscle

Oxidative Stress Reprograms Lipopolysaccharide Signaling via Src Kinase-dependent Pathway in RAW 264.7 Macrophage Cell Line

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