Aconitase: Sensitive target and measure of superoxide

Gardner, Paul R.

doi:10.1016/s0076-6879(02)49317-2

Cited by 266 publications

(228 citation statements)

References 41 publications

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“…In vitro studies with purified protein have demonstrated that aconitase can be inactivated through oxidant-induced release of a labile ␣-Fe from the enzyme's [4Fe-4S] 2ϩ cluster (16)(17)(18)(19). Additionally, the Lon protease was shown to degrade aconitase that had undergone extensive oxidative modification (23).…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondria, a major subcellular source of oxygen radicals during reperfusion, exhibit decrements in activity attributed, in part, to oxidative modifications to key metabolic enzymes (10). Aconitase and ␣-ketoglutarate dehydrogenase, which are known to be susceptible to oxidative inactivation in vitro (11)(12)(13)(14)(15)(16)(17)(18)(19) have been reported to decline in activity during in vivo cardiac ischemia͞ reperfusion (20).…”

mentioning

confidence: 99%

“…Loss in aconitase activity is commonly used as a biomarker of oxidative damage due to the susceptibility of the enzyme's [4Fe-4S] 2ϩ cubane cluster to oxidative disassembly (16)(17)(18)(19). Nevertheless, we have recently shown that, when mitochondria are exposed to H 2 O 2 in vitro, aconitase can undergo oxidative inhibition followed by reactivation upon resolution of the oxidative stress (15).…”

mentioning

confidence: 99%

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Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion

Bulteau

Lundberg

Ikeda‐Saito

et al. 2005

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

127

113

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Prooxidents can induce reversible inhibition or irreversible inactivation and degradation of the mitochondrial enzyme aconitase. Cardiac ischemia͞reperfusion is associated with an increase in mitochondrial free radical production. In the current study, the effects of reperfusion-induced production of prooxidants on mitochondrial aconitase and proteolytic activity were determined to assess whether alterations represented a regulated response to changes in redox status or oxidative damage. Evidence is provided that ATP-dependent proteolytic activity increased during early reperfusion followed by a time-dependent reduction in activity to control levels. These alterations in proteolytic activity paralleled an increase and subsequent decrease in the level of oxidatively modified protein. In vitro data supports a role for prooxidants in the activation of ATP-dependent proteolytic activity. Despite inhibition during early periods of reperfusion, aconitase was not degraded under the conditions of these experiments. Aconitase activity exhibited a decline in activity followed by reactivation during cardiac reperfusion. Loss and regain in activity involved reversible sulfhydryl modification. Aconitase was found to associate with the iron binding protein frataxin exclusively during reperfusion. In vitro, frataxin has been shown to protect aconitase from [4Fe-4S] 2؉ cluster disassembly, irreversible inactivation, and, potentially, degradation. Thus, the response of mitochondrial aconitase and ATP-dependent proteolytic activity to reperfusioninduced prooxidant production appears to be a regulated event that would be expected to reduce irreparable damage to the mitochondria.H ighly reactive oxygen derived free radicals, such as superoxide anion (O 2•Ϫ ) and the prooxidant hydrogen peroxide (H 2 O 2 ), can interact with a variety of cellular components, altering both structure and function (1). Although evidence for these reactions has long been sought as indication of free radical involvement in degenerative disorders, recent evidence indicates that these processes also participate in the regulation of cellular function (1, 2). This finding is exemplified by the discovery of enzymatic systems, such as thioredoxin reductase͞thioredoxin (3), glutaredoxin (4), methione sulfoxide reductase (5), and sulfiredoxin (6), which catalyze reversal of oxidative modifications to protein and restoration of protein function. Additionally, receptor-and enzyme-mediated systems exist that catalyze the production of free radicals in response to changes in extracellular and intracellular factors (1, 2). It is therefore important that free radicals produced during physiological and pathophysiological conditions be investigated not simply for their potential to carry out damaging processes but also to induce appropriate alterations in response to changes in cellular homeostasis.Reduction and͞or cessation of blood f low to myocardial tissue, termed ischemia, occurs primarily as a result of formation of atherosclerotic lesions in the coronary arteries...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion

Bulteau

Lundberg

Ikeda‐Saito

et al. 2005

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

127

113

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“…Mitochondria were solubilized in 1% Triton X-100 (40 -60 g for aconitase and 7-9 g mitochondrial protein for superoxide dismutase [SOD]). Aconitase specific activity was measured in a medium containing 30 mmol/l sodium citrate, 0.6 mmol/l MnCl 2 , 0.2 mmol/l NADP, 50 mmol/l Tris-HCl, pH 7.4, and 2 units isocitrate dehydrogenase, and the formation of NADPH was followed spectrophotometrically (340 nm) at 25°C (20). SOD specific activity was measured in a medium containing 0.1 mmol/l EDTA, 2 mmol/l KCN, 50 mmol/l KH 2 PO 4 , pH 7.8, 20 mmol/l cythocrome c, 0.1 mmol/l xanthyne, and 0.01 unit xanthyne oxidase.…”

Section: Methodsmentioning

confidence: 99%

Altered Skeletal Muscle Subsarcolemmal Mitochondrial Compartment During Catch-Up Fat After Caloric Restriction

et al. 2006

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An accelerated rate of fat recovery (catch-up fat) and insulin resistance are characteristic features of weight recovery after caloric restriction, with implications for the pathophysiology of catch-up growth and weight fluctuations. Using a previously described rat model of weight recovery in which catch-up fat and skeletal muscle insulin resistance have been linked to suppressed thermogenesis per se, we investigated alterations in mitochondrial energetics and oxidative stress in subsarcolemmal (SS) and intermyofibrillar (IMF) skeletal muscle mitochondria. After 2 weeks of semistarvation followed by 1 week of refeeding, the refed rats show persistent and selective reductions in SS mitochondrial mass (assessed from citrate synthase activity in tissue homogenate and isolated mitochondria) and oxidative capacity. Furthermore, the refed rats show, in both SS and IMF muscle mitochondria, a lower aconitase activity (whose inactivation is an index of increased reactive oxygen species [ROS]), associated with higher superoxide dismutase activity and increased proton leak. Taken together, these studies suggest that diminished skeletal muscle mitochondrial mass and function, specifically in the SS mitochondrial compartment, contribute to the high metabolic efficiency for catch-up fat after caloric restriction and underscore a potential link between diminished skeletal muscle SS mitochondrial energetics, increased ROS concentration, and insulin resistance during catch-up fat. Diabetes

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“…•Ϫ generation (12). Therefore, we monitored aconitase enzyme activity in carotid bodies from CIH and control animals.…”

Section: Evidence For the Involvement Of Omentioning

confidence: 99%

Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: Implications for recurrent apneas

Peng

Overholt

Kline

et al. 2003

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

403

631

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Reflexes from the carotid body have been implicated in cardiorespiratory disorders associated with chronic intermittent hypoxia (CIH). To investigate whether CIH causes functional and͞or structural plasticity in the carotid body, rats were subjected to 10 days of recurrent hypoxia or normoxia. Acute exposures to 10 episodes of hypoxia evoked long-term facilitation (LTF) of carotid body sensory activity in CIH-conditioned but not in control animals. The magnitude of sensory LTF depended on the length of CIH conditioning and was completely reversible and unique to CIH, because conditioning with a comparable duration of sustained hypoxia was ineffective. Histological analysis revealed no differences in carotid body morphology between control and CIH animals. Previous treatment with superoxide anion (O 2•؊ ) scavenger prevented sensory LTF. In the CIH-conditioned animals, carotid body aconitase enzyme activity decreased compared with controls. These observations suggest that increased generation of reactive oxygen species contribute to sensory LTF. In CIH animals, carotid body complex I activity of the mitochondrial electron transport is inhibited, suggesting mitochondria as one source of O 2•؊ generation. These observations demonstrate that CIH induces a previously uncharacterized form of reactive oxygen species-dependent, reversible, functional plasticity in carotid body sensory activity. The sensory LTF may contribute to persistent reflex activation of sympathetic nerve activity and blood pressure in recurrent apnea patients experiencing CIH.H ypoxia is a pervasive physiological stimulus. Changes in arterial blood oxygen levels are monitored continuously by peripheral chemoreceptors, especially the carotid bodies (reviewed in ref. 1). The ensuing reflexes are critical for maintaining homeostasis during hypoxia. Hypoxia is encountered under many different circumstances. For instance, sojourn to high altitude exposes individuals to sustained hypoxia (SH). On the other hand, people living at sea level experience intermittent hypoxia more often in life than SH. Many pathophysiological situations including recurrent apnea syndromes (central or obstructive sleep apneas), apneas in premature infants, and asthmatic attacks are associated with intermittent hypoxia. Decreases in arterial blood oxygen occur in both types of hypoxia. However, cardiorespiratory systems adapt to chronic SH to maintain adequate oxygen delivery to tissues (reviewed in refs. 2 and 3), whereas chronic intermittent hypoxia (CIH) leads to serious pathophysiological consequences such as hypertension, myocardial infarcts, and even stroke (4, 5).Reflexes from the carotid body have been proposed to play a critical role in ventilatory and circulatory adaptations to chronic SH and are associated with structural changes in the carotid body including hypertrophy of the organ, increased vascularization, and increased number of glomus cells (the putative oxygensensing cells; reviewed in refs. 2 and 3). There is evidence that reflexes arising from the carotid ...

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Aconitase: Sensitive target and measure of superoxide

Cited by 266 publications

References 41 publications

Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion

Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion

Altered Skeletal Muscle Subsarcolemmal Mitochondrial Compartment During Catch-Up Fat After Caloric Restriction

Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: Implications for recurrent apneas

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