Oxygen Radicals Can Induce Preconditioning in Rabbit Hearts

Tritto, Isabella; D’Andrea, Davide; Eramo, Nicola; Scognamiglio, Annalisa; Simone, Ciro De; Violante, A.; Esposito, Annamaria; Chiariello, Massimo; Ambrosio, Giuseppe

doi:10.1161/01.res.80.5.743

Cited by 259 publications

(165 citation statements)

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“…Preconditioning, a series of brief periods of ischemia and reperfusion, protects the myocardium from deleterious events associated with extended durations of ischemia and reperfusion (7)(8)(9). Cardioprotection afforded by preconditioning appears mediated, in part, by the production of oxygen radicals (35)(36)(37)(38)(39)(40) and is associated with reductions in Ca 2ϩ overload (7,(41)(42)(43) and free radical production (44) during extended periods of ischemia͞ reperfusion.…”

Section: Discussionmentioning

confidence: 99%

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.

129

118

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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%

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.

129

118

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“…Moreover, mitochondrial connexin-43 has also been implicated in ROS signaling although its role is not completely defined (14)(15)(16). A target of ROS in redox signaling is the PKC (possibly PKCe2); in fact hearts can be preconditioned by simply infusing free radicals into the coronary arteries and that protection can be blocked by a PKC antagonist (184). Indeed, it has been reported that ROS can activate PKC in vitro by reacting with thiol groups associated with the zinc finger region of the molecule (98).…”

Section: Interaction Between Redox Environment and Cardioprotective Pmentioning

confidence: 99%

“…At reperfusion, O 2 À and other ROS may strongly oxidize the cardiomyocytes already damaged by the ischemia, thus favoring cell death (1,2,53,116,183,184 in myocardial injury (10-12, 52, 135, 165). In particular, high ONOO À concentrations are considered to be highly cytotoxic (11,12,135,165).…”

Section: Introductionmentioning

confidence: 99%

Cardioprotective Pathways During Reperfusion: Focus on Redox Signaling and Other Modalities of Cell Signaling

Pagliaro

Moro

Tullio

et al. 2011

Antioxidants & Redox Signaling

114

152

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Post-ischemic reperfusion may result in reactive oxygen species (ROS) generation, reduced availability of nitric oxide (NO ), Ca 2+ overload, prolonged opening of mitochondrial permeability transition pore, and other processes contributing to cell death, myocardial infarction, stunning, and arrhythmias. With the discovery of the preconditioning and postconditioning phenomena, reperfusion injury has been appreciated as a reality from which protection is feasible, especially with postconditioning, which is under the control of physicians. Potentially cooperative protective signaling cascades are recruited by both pre-and postconditioning. In these pathways, phosphorylative= dephosphorylative processes are widely represented. However, cardioprotective modalities of signal transduction also include redox signaling by ROS, S-nitrosylation by NO and derivative, S-sulfhydration by hydrogen sulfide, and O-linked glycosylation with beta-N-acetylglucosamine. All these modalities can interact and regulate an entire pathway, thus influencing each other. For instance, enzymes can be phosphorylated and=or nitrosylated in specific and=or different site(s) with consequent increase or decrease of their specific activity. The cardioprotective signaling pathways are thought to converge on mitochondria, and various mitochondrial proteins have been identified as targets of these post-transitional modifications in both pre-and postconditioning. Antioxid. Redox Signal. 14, 833-850.

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“…Recent studies suggested that free radicals, which directly stimulate phospholipases in cells, also contribute to triggering preconditioning in the rabbit model. [191][192][193] Evidence also suggests that at least one tyrosine kinase that also may be involved in the mechanism of preconditioning exists downstream from PKC in the rabbit heart. 194 Similar findings were observed in a model of isolated rabbit cardiomyocytes developed by Armstrong et al 195,196 They assessed myocyte injury as the rate of development of osmotic fragility during prolonged ischemic pelleting of cells incubated under oil.…”

Section: Mechanism Of Preconditioningmentioning

confidence: 99%