Lung manganese superoxide dismutase increases during cytokine-mediated protection against pulmonary oxygen toxicity in rats.

Lewis-Molock, Yvette; Suzuki, Kunihiro; Taniguchi, N; Nguyen, Dee Dee; Mason, Robert J.; White, Carl W.

doi:10.1165/ajrcmb.10.2.8110468

Cited by 46 publications

(17 citation statements)

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“…However, different tissues responded differently; skeletal muscle dramatically induced Sod2, whereas heart increased Sod2 only modestly, even though both tissues increased Gpx1 levels similarly. These results recapitulate previous work in which Sod2 mRNA (26,27), protein (26)(27)(28), and Gpx1 mRNA and activity (29) were found to be induced in response to oxidative stress. Also, Gpx1 activity was found to be increased in cultured cells overexpressing Sod2 (30).…”

Section: Discussionsupporting

confidence: 90%

Mitochondrial disease in mouse results in increased oxidative stress

Esposito

Melov

Panov

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

566

340

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It has been hypothesized that a major factor in the progression of mitochondrial disease resulting from defects in oxidative phosphorylation (OXPHOS) is the stimulation of the mitochondrial production of reactive oxygen species (ROS) and the resulting damage to the mtDNA. To test this hypothesis, we examined the mitochondria from mice lacking the heart͞muscle isoform of the adenine nucleotide translocator (Ant1), designated Ant1 tm2Mgr (؊͞؊) mice. The absence of Ant1 blocks the exchange of ADP and ATP across the mitochondrial inner membrane, thus inhibiting OXPHOS. Consistent with Ant1 expression, mitochondria isolated from skeletal muscle, heart, and brain of the Ant1-deficient mice produced markedly increased amounts of the ROS hydrogen peroxide, whereas liver mitochondria, which express a different Ant isoform, produced normally low levels of hydrogen peroxide. The increased production of ROS by the skeletal muscle and heart was associated with a dramatic increase in the ROS detoxification enzyme manganese superoxide dismutase (Sod2, also known as MnSod) in muscle tissue and muscle mitochondria, a modest increase in Sod2 in heart tissue, and no increase in heart mitochondria. The level of glutathione peroxidase-1 (Gpx1), a second ROS detoxifying enzyme, was increased moderately in the mitochondria of both tissues. Consistent with the lower antioxidant defenses in heart, the heart mtDNAs of the Ant1-deficient mice showed a striking increase in the accumulation of mtDNA rearrangements, whereas skeletal muscle, with higher antioxidant defenses, had fewer mtDNA rearrangements. Hence, inhibition of OXPHOS does increase mitochondrial ROS production, eliciting antioxidant defenses. If the antioxidant defenses are insufficient to detoxify the ROS, then an increased mtDNA mutation rate can result.

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Section: Discussionsupporting

confidence: 90%

Mitochondrial disease in mouse results in increased oxidative stress

Esposito

Melov

Panov

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

566

340

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“…Endotoxemia stimulates glucose uptake in all macrophage-rich tissues, including lung, spleen, and intestine [79]. The fact that lung shows the most marked increase in glucose use after LPS, and that LPS pretreatment ameliorates oxygen toxicity in the lung [80,81] suggest that the upregulated glucose metabolism may support HMS-dependent ROS detoxification in this organ as well. Taken together, these investigations reveal that, during the host response to infection, the elevated glucose use by the liver serves not only the increased energy need but also supports glucose-dependent ROS metabolism.…”

Section: Endotoxemia and The Intercellular Oxidant Balancementioning

confidence: 99%

Endotoxemia, pentose cycle, and the oxidant/antioxidant balance in the hepatic sinusoid

Spolarics

1998

Journal of Leukocyte Biology

115

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During the innate immune response, excessive release of reactive oxygen species (ROS) from sequestered phagocytes and activated resident macrophages represents the predominant component of oxidative stress in the liver and other tissues. The consequence of oxidative stress is determined by the status and adaptive changes of antioxidant pathways. In this review, we present evidence that the synchronized response of hepatic sinusoidal endothelial cells, the primary sites of phagocyte attachment, plays an important role in defense against phagocyte-derived ROS. An essential component of the metabolic adaptation of hepatic sinusoidal cells to lipopolysaccharide (LPS)-induced oxidative stress is the stimulated expression of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the pentose cycle (hexose monophosphate shunt, HMS). All major ROS-metabolic enzymes, i.e., glutathione peroxidase, glutathione reductase, catalase, superoxide dismutases, NADPH oxidase, and nitric oxide synthase, directly or indirectly depend on NADPH, which is produced in the HMS in these cells. The functional significance of up-regulated HMS within a particular cell type depends on the accompanying adaptive changes in ROS-metabolizing enzymes. In LPS-activated Kupffer cells, the elevated expression of glucose transporter GLUT1 and G6PD mainly serves primed production of superoxide anion, hydrogen peroxide, and nitric oxide. In sinusoidal endothelial cells, the LPS-induced response pattern of glucose-and ROS-metabolizing enzymes results in elevated ROS detoxifying capacity. The described studies also suggest the existence of an intercellular oxidant balance between prooxidant Kupffer cells and antioxidant endothelial cells in the hepatic micro-environment. Maintenance of the intercellular oxidant/antioxidant balance between phagocytes and endothelial cells may represent an important mechanism protecting the hepatic parenchyma against exogenous oxidative stress during the inflammatory response. J. Leukoc. Biol. 63: 534-541; 1998.

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“…Of the antioxidant enzymes, MnSOD is uniquely induced in response to conditions of oxidative stress (2,26,53), emphasizing the importance of protecting the energy-producing machinery within the mitochondria from oxidative damage. Both TNF and IL-1 induce intracellular superoxide generation, which probably contributes to their cytolytic activity (41,54).…”

mentioning

confidence: 99%

“…The role of MnSOD in protection from oxidative damage and the cytolytic effects of TNF was demonstrated by the discovery that overexpression of MnSOD in some TNF-sensitive cell lines conferred resistance to TNF-mediated apoptosis (52). Additionally, TNF-and IL-1-mediated induction of MnSOD has been shown to confer protection against myocardial reperfusion injury (34,35) and tissue damage due to oxidative stress (26,43). The mechanisms for the induction of MnSOD expression under all of these conditions are poorly understood.…”

mentioning

confidence: 99%