Hydroxynonenal and uncoupling proteins: A model for protection against oxidative damage

Echtay, Karim S.; Pakay, Julian L.; Esteves, Telma C.; Brand, Martin D.

doi:10.1002/biof.5520240114

Cited by 59 publications

(46 citation statements)

References 83 publications

(111 reference statements)

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“…The mechanism of induction of proton leak by HNE is unclear. It has been suggested that HNE may induce covalent modification and conformational changes in the UCPs that allow the passage of protons back into the mitochondrial matrix (95). Both UCP2 and 3 are expressed in the heart, but their role is unclear.…”

Section: Mitochondrial Uncoupling Proteinsmentioning

confidence: 99%

Mitochondrial Pathways, Permeability Transition Pore, and Redox Signaling in Cardioprotection: Therapeutic Implications

Penna

Perrelli²,

Pagliaro³

2013

Antioxidants & Redox Signaling

145

133

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Reperfusion therapy is the indispensable treatment of acute myocardial infarction (AMI) and must be applied as soon as possible to attenuate the ischemic insult. However, reperfusion is responsible for additional myocardial damage likely involving opening of the mitochondrial permeability transition pore (mPTP). A great part of reperfusion injury occurs during the first minute of reperfusion. The prolonged opening of mPTP is considered one of the endpoints of the cascade to myocardial damage, causing loss of cardiomyocyte function and viability. Opening of mPTP and the consequent oxidative stress due to reactive oxygen and nitrogen species (ROS/RNS) are considered among the major mechanisms of mitochondrial and myocardial dysfunction. Kinases and mitochondrial components constitute an intricate network of signaling molecules and mitochondrial proteins, which interact in response to stressors. Cardioprotective pathways are activated by stimuli such as preconditioning and postconditioning (PostC), obtained with brief intermittent ischemia or with pharmacological agents, which drastically reduce the lethal ischemia/reperfusion injury. The protective pathways converging on mitochondria may preserve their function. Protection involves kinases, adenosine triphosphate-dependent potassium channels, ROS signaling, and the mPTP modulation. Some clinical studies using ischemic PostC during angioplasty support its protective effects, and an interesting alternative is pharmacological PostC. In fact, the mPTP desensitizer, cyclosporine A, has been shown to induce appreciable protections in AMI patients. Several factors and comorbidities that might interfere with cardioprotective signaling are considered. Hence, treatments adapted to the characteristics of the patient (i.e., phenotype oriented) might be feasible in the future. Antioxid. Redox Signal. 00, 000-000.

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Section: Mitochondrial Uncoupling Proteinsmentioning

confidence: 99%

Mitochondrial Pathways, Permeability Transition Pore, and Redox Signaling in Cardioprotection: Therapeutic Implications

Penna

Perrelli²,

Pagliaro³

2013

Antioxidants & Redox Signaling

145

133

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“…The central nervous system is particularly vulnerable to oxidative stress, owing to its high rate of oxygen utilization and abundance of unsaturated lipids. Thus, a great deal of attention has been focussed on the possible roles of lipid peroxidation-derived aldehydes in terms of their contributions to neuronal dysfunction in oxidative stress-associated neurodegenerative disorders (25).…”

Section: Participation Of Iron Ions In the Ferritin/h2o2-mediated Lipmentioning

confidence: 99%

Reaction of ferritin with hydrogen peroxide induces lipid peroxidation

Yoon¹,

Lee²,

Kang³

2010

BMB Reports

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Lipid peroxidation is known to be an important factor in the pathologies of many diseases associated with oxidative stress. We assessed the lipid peroxidation induced by the reaction of ferritin with H2O2. When linoleic acid micelles or phosphatidyl choline liposomes were incubated with ferritin and H2O2, lipid peroxidation increased in the presence of ferritin and H2O2 in a concentration-dependent manner. The hydroxyl radical scavengers, azide and thiourea, prevented lipid peroxidation induced by the ferritin/H2O2 system. The iron specific chelator desferoxamine also prevented ferritin/H2O2 systemmediated lipid peroxidation. These results demonstrate the possible role of iron in ferritin/H2O2 system-mediated lipid peroxidation. Carnosine is involved in many cellular defense processes, including free radical detoxification. In this study, carnosine, homocarnosine, and anserine were shown to significantly prevent ferritin/H2O2 system-mediated lipid peroxidation and also inhibited the free radical-generation activity of ferritin. These results indicated that carnosine and related compounds may prevent ferritin/H2O2 system-mediated lipid peroxidation via free radical scavenging. [BMB reports 2010; 43(3): 219-224]

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“…The underlying processes leading to the acute and chronic FA-induced increase in workindependent MV O 2 are far from clear. First, increased MV O 2 may be related to the following: 1) increased myocardial FA oxidation rate (accompanying the elevated FA supply), leading to increased oxygen cost due to the lower ratio of ATP produced to oxygen consumed (P/O ratio), accompanying FA oxidation (43); 2) FA and FA derivatives induce increased mitochondrial reactive oxygen species (ROS) production and activate uncoupling proteins (UCP) (15,25); and 3) FAinduced futile cycling, such as FA-triacylglycerol cycling (42). In addition, there are reasons to believe that FAs or FAmediated changes may influence Ca 2ϩ handling.…”

mentioning

confidence: 99%

Chronic and acute exposure of mouse hearts to fatty acids increases oxygen cost of excitation-contraction coupling

Boardman

Larsen

Severson

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Boardman NT, Larsen TS, Severson DL, Essop MF, Aasum E. Chronic and acute exposure of mouse hearts to fatty acids increases oxygen cost of excitation-contraction coupling. Am J Physiol Heart Circ Physiol 300: H1631-H1636, 2011. First published February 18, 2011 doi:10.1152/ajpheart.01190.2010The aim of the present study was to evaluate the underlying processes involved in the oxygen wasting induced by inotropic drugs and acute and chronic elevation of fatty acid (FA) supply, using unloaded perfused mouse hearts from normal and type 2 diabetic (db/db) mice. We found that an acute elevation of the FA supply in normal hearts, as well as a chronic (in vivo) exposure to elevated FA as in db/db hearts, increased myocardial oxygen consumption (MV O2unloaded) due to increased oxygen cost for basal metabolism and for excitation-contraction (EC) coupling. Isoproterenol stimulation, on top of a high FA supply, led to an additive increase in MV O2unloaded, because of a further increase in oxygen cost for EC coupling. In db/db hearts, the acute elevation of FA did not further increase MV O2. Since the elevation in the FA supply is accompanied by increased rates of myocardial FA oxidation, the present study compared MV O2 following increased FA load versus FA oxidation rate by exposing normal hearts to normal and high FA concentration (NF and HF, respectively) and to compounds that either stimulate (GW-610742) or inhibit [dichloroacetate (DCA)] FA oxidation. While HF and NF ϩ GW-610742 increased FA oxidation to the same extent, only HF increased MV O2unloaded. Although DCA counteracted the HF-induced increase in FA oxidation, DCA did not reduce MV O2unloaded. Thus, in normal hearts, acute FA-induced oxygen waste is 1) due to an increase in the oxygen cost for both basal metabolism and EC coupling and 2) not dependent on the myocardial FA oxidation rate per se, but on processes initiated by the presence of FAs. In diabetic hearts, chronic exposure to elevated circulating FAs leads to adaptations that afford protection against the detrimental effect of an acute FA load, suggesting different underlying mechanisms behind the increased MV O2 following acute and chronic FA load. cardiac efficiency; myocardial oxygen consumption; fatty acid oxidation; basal metabolism; isoproterenol SEVERAL PHYSIOLOGICAL AND pathophysiological conditions (including fasting, diabetes/obesity, postoperatively) are associated with elevated levels of circulating catecholamines and fatty acid (FA). Both conditions are known to increase myocardial oxygen consumption (MV O 2 ) more than would be expected by changes in cardiac work, leading to oxygen waste and thus decreased cardiac efficiency (27,38,44,50).Following chronic elevation of circulating lipids such as in diabetes and obesity, FA becomes the predominant fuel for ATP generation in the heart both due to elevated supply and transcriptional changes increasing the expression of genes associated with FA utilization (1, 4, 5). Altered myocardial substrate supply and decreased cardiac efficiency have b...

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Hydroxynonenal and uncoupling proteins: A model for protection against oxidative damage

Cited by 59 publications

References 83 publications

Mitochondrial Pathways, Permeability Transition Pore, and Redox Signaling in Cardioprotection: Therapeutic Implications

Mitochondrial Pathways, Permeability Transition Pore, and Redox Signaling in Cardioprotection: Therapeutic Implications

Reaction of ferritin with hydrogen peroxide induces lipid peroxidation

Chronic and acute exposure of mouse hearts to fatty acids increases oxygen cost of excitation-contraction coupling

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