The modulation of ferryl myoglobin formation and its oxidative effects on low density lipoproteins by nitric oxide

Dee, Gareth; Rice‐Evans, Catherine; Obeyesekera, Sharmin; Meraji, Shokoufeh; Jacobs, Michael; Bruckdorfer, K. Richard

doi:10.1016/0014-5793(91)81338-9

Cited by 92 publications

(34 citation statements)

References 19 publications

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“…Interestingly, nitric oxide also partially protects against the renal failure (23). In accord with our hypothesis, this might be explained by an effect of nitric oxide to inhibit heme-dependent lipid peroxidation (24).…”

supporting

confidence: 87%

A Causative Role for Redox Cycling of Myoglobin and Its Inhibition by Alkalinization in the Pathogenesis and Treatment of Rhabdomyolysis-induced Renal Failure

Moore¹,

Holt²,

Patel³

et al. 1998

Journal of Biological Chemistry

250

222

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Muscle injury (rhabdomyolysis) and subsequent deposition of myoglobin in the kidney causes renal vasoconstriction and renal failure. We tested the hypothesis that myoglobin induces oxidant injury to the kidney and the formation of F 2 -isoprostanes, potent renal vasoconstrictors formed during lipid peroxidation. In low density lipoprotein (LDL), myoglobin induced a 30-fold increase in the formation of F 2 -isoprostanes by a mechanism involving redox cycling between ferric and ferryl forms of myoglobin. In an animal model of rhabdomyolysis, urinary excretion of F 2 -isoprostanes increased by 7.3-fold compared with controls. Administration of alkali, a treatment for rhabdomyolysis, improved renal function and significantly reduced the urinary excretion of F 2 -isoprostanes by ϳ80%. EPR and UV spectroscopy demonstrated that myoglobin was deposited in the kidneys as the redox competent ferric myoglobin and that it's concentration was not decreased by alkalinization. Kinetic studies demonstrated that the reactivity of ferryl myoglobin, which is responsible for inducing lipid peroxidation, is markedly attenuated at alkaline pH. This was further supported by demonstrating that myoglobin-induced oxidation of LDL was inhibited at alkaline pH. These data strongly support a causative role for oxidative injury in the renal failure of rhabdomyolysis and suggest that the protective effect of alkalinization may be attributed to inhibition of myoglobin-induced lipid peroxidation.

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supporting

confidence: 87%

A Causative Role for Redox Cycling of Myoglobin and Its Inhibition by Alkalinization in the Pathogenesis and Treatment of Rhabdomyolysis-induced Renal Failure

Moore¹,

Holt²,

Patel³

et al. 1998

Journal of Biological Chemistry

250

222

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“…Both species are strong oxidants, which may induce lipid and protein peroxidation. The heme to protein cross-linked form of myoglobin, generated from interaction of the ferryl heme with the radical, represents the more cytotoxic form than ferryl myoglobin and oxidizes free and membrane-bound lipids (38). Irrespective of this discussion, our current data show that myoglobin, via reduction of nitrite to NO • , attenuates the infarct size after I/R both ex vivo and in vivo.…”

Section: Discussionmentioning

confidence: 60%

Nitrite reductase activity of myoglobin regulates respiration and cellular viability in myocardial ischemia-reperfusion injury

Hendgen‐Cotta

Merx

Shiva

et al. 2008

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

371

353

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The nitrite anion is reduced to nitric oxide (NO • ) as oxygen tension decreases. Whereas this pathway modulates hypoxic NO • signaling and mitochondrial respiration and limits myocardial infarction in mammalian species, the pathways to nitrite bioactivation remain uncertain. Studies suggest that hemoglobin and myoglobin may subserve a fundamental physiological function as hypoxia dependent nitrite reductases. Using myoglobin wild-type ( +/+ ) and knockout ( −/− ) mice, we here test the central role of myoglobin as a functional nitrite reductase that regulates hypoxic NO • generation, controls cellular respiration, and therefore confirms a cytoprotective response to cardiac ischemia-reperfusion (I/R) injury. We find that myoglobin is responsible for nitrite-dependent NO • generation and cardiomyocyte protein iron-nitrosylation. Nitrite reduction to NO • by myoglobin dynamically inhibits cellular respiration and limits reactive oxygen species generation and mitochondrial enzyme oxidative inactivation after I/R injury. In isolated myoglobin +/+ but not in myoglobin −/− hearts, nitrite treatment resulted in an improved recovery of postischemic left ventricular developed pressure of 29%. In vivo administration of nitrite reduced myocardial infarction by 61% in myoglobin +/+ mice, whereas in myoglobin −/− mice nitrite had no protective effects. These data support an emerging paradigm that myoglobin and the heme globin family subserve a critical function as an intrinsic nitrite reductase that regulates responses to cellular hypoxia and reoxygenation. myoglobin knockout mice

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“…In agreement with the hypothesis that NO is part of the system controlling Fe uptake in the first instance of exposure, we showed that NO content in DG was drastically decreased by day 2 of treatment. On the other hand, NO has previously been shown to inhibit lipid peroxidation in many biological systems (Dee et al, 1991;Kanner et al, 1991;Hogg et al, 1993;Rubbo et al, 1994;Gorbunov et al, 1995;Sharpe et al, 2003) through its ability of binding catalytically active Fe (Radi et al, 1995). Thus, the decreased NO content in DG measured by day 2 of exposure to excess Fe could also play a role in the increase in lipid peroxidation, as previously proposed for other biological systems (Radi et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Exposure to excess dissolved iron in vivo affects oxidative status in the bivalve Mya arenaria

González

Abele

Puntarulo

2010

Comparative Biochemistry and Physiology Part C: Toxicology &

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The effect of in vivo Fe exposure on the oxidative metabolism of the bivalve Mya arenaria was studied. Fe was supplemented in natural seawater and resulted in a significant increase in the total Fe content in the bivalve digestive gland (DG) between 9 to 17 days of exposure. Mortality of treated animals increased drastically after day 18. Oxidative stress conditions were characterized in DG through assessment of the generation of reactive oxygen species (ROS) and ascorbyl radical (A•) content. Both parameters were affected following a biphasic profile showing significant increases by days 2 and 9 of Fe exposure. The content of 2-thiobarbituric acid reactive substances (TBARS) was significantly increased over control values by days 2, 9 and 17 of treatment. The labile Fe pool (LIP) in isolated DG was elevated over control values by day 7, and maintained this increase until day 17 of Fe exposure. The content of NO, assessed by EPR spin trapping, was 60% lower in DG of animals exposed for 2 days to Fe than in control values, with no further changes. The biphasic profile of oxidative stress response to Fe exposure in DG suggests that at early stages of Fe supplementation the cellular control mechanisms, such as CAT activity, were operative to limit oxidative damage, but further Fe exposure overwhelmed these abilities. Moreover, the second phase could be understood as the consequence of the exhaustion of cellular protective systems that could also involve NO.

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The modulation of ferryl myoglobin formation and its oxidative effects on low density lipoproteins by nitric oxide

Cited by 92 publications

References 19 publications

A Causative Role for Redox Cycling of Myoglobin and Its Inhibition by Alkalinization in the Pathogenesis and Treatment of Rhabdomyolysis-induced Renal Failure

A Causative Role for Redox Cycling of Myoglobin and Its Inhibition by Alkalinization in the Pathogenesis and Treatment of Rhabdomyolysis-induced Renal Failure

Nitrite reductase activity of myoglobin regulates respiration and cellular viability in myocardial ischemia-reperfusion injury

Exposure to excess dissolved iron in vivo affects oxidative status in the bivalve Mya arenaria

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