The Radical Trap 5,5-Dimethyl-1-Pyrroline<i>N</i>-Oxide Exerts Dose-Dependent Protection against Myocardial Ischemia-Reperfusion Injury through Preservation of Mitochondrial Electron Transport

Zuo, Li; Chen, Yeong Renn; Reyes, Levy; Lee, Hsin Ling; Chen, Chwen Lih; Villamena, Frederick A.; Zweíer, Jay L.

doi:10.1124/jpet.108.143479

Cited by 47 publications

(54 citation statements)

References 46 publications

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“…In fact, there are some promising indications that cyclophilin D inhibitors, such as cyclosporine, could reduce infarct size in humans [38,39]. However, limiting oxidative stress during reperfusion will help to contain the mitochondrial damage and the recovery of the surviving cells [40].…”

Section: +mentioning

confidence: 99%

The role of mitochondria in cardiac development and protection

Pohjoismäki

Goffart

2017

Free Radical Biology and Medicine

106

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Mitochondria are essential for the development as well as maintenance of the myocardium, the most energy consuming tissue in the human body. Mitochondria are not only a source of ATP energy but also generators of reactive oxygen species (ROS), that cause oxidative damage, but also regulate physiological processes such as the switch from hyperplastic to hypertrophic growth after birth. As excess ROS production and oxidative damage are associated with cardiac pathology, it is not surprising that much of the research focused on the deleterious aspects of free radicals. However, cardiomyocytes are naturally highly adapted against repeating oxidative insults, with evidence suggesting that moderate and acute ROS exposure has beneficial consequences for mitochondrial maintenance and cardiac health. Antioxidant defenses, mitochondrial quality control, mtDNA maintenance mechanisms as well as mitochondrial fusion and fission improve mitochondrial function and cardiomyocyte survival under stress conditions. As these adaptive processes can be induced, promoting mitohormesis or mitochondrial biogenesis using controlled ROS exposure could provide a promising strategy to increase cardiomyocyte survival and prevent pathological remodeling of the myocardium.

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Section: +mentioning

confidence: 99%

The role of mitochondria in cardiac development and protection

Pohjoismäki

Goffart

2017

Free Radical Biology and Medicine

106

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“…Generally, it is a good idea to measure ROS by two independent methods and monitor different species in the same samples. A wide variety of spin traps and spin probes such as DMPO, PBN, TEMPOL, and mito-TEMPO protect the brain, heart, and vascular tissue under conditions of oxidative stress (8,19,64). Beneficial responses to these agents have been used to implicate ROS in various pathophysiological conditions.…”

Section: Antioxidant Activity Of Ros Probesmentioning

confidence: 99%

Methods for Detection of Mitochondrial and Cellular Reactive Oxygen Species

Dikalov

Harrison

2014

Antioxidants & Redox Signaling

536

421

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Significance: Mitochondrial and cellular reactive oxygen species (ROS) play important roles in both physiological and pathological processes. Different ROS, such as superoxide (O 2 -), hydrogen peroxide, and peroxynitrite (ONOO e ), stimulate distinct cell-signaling pathways and lead to diverse outcomes depending on their amount and subcellular localization. A variety of methods have been developed for ROS detection; however, many of these methods are not specific, do not allow subcellular localization, and can produce artifacts. In this review, we will critically analyze ROS detection and present advantages and the shortcomings of several available methods. Recent Advances: In the past decade, a number of new fluorescent probes, electron-spin resonance approaches, and immunoassays have been developed. These new state-of-the-art methods provide improved selectivity and subcellular resolution for ROS detection. Critical Issues: Although new methods for HPLC superoxide detection, application of fluorescent boronate-containing probes, use of cell-targeted hydroxylamine spin probes, and immunospin trapping have been available for several years, there has been lack of translation of these into biomedical research, limiting their widespread use. Future Directions: Additional studies to translate these new technologies from the test tube to physiological applications are needed and could lead to a wider application of these approaches to study mitochondrial and cellular ROS. Antioxid. Redox Signal. 20, 372-382.

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“…ROS have been documented as a general response to ischemia-reperfusion injury (26,43), muscle stimulation (29), and heat stress (44). Excessive ROS disrupt nearly all physiological systems (1,44,46,47,49,50).…”

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Low Po₂conditions induce reactive oxygen species formation during contractions in single skeletal muscle fibers

Zuo

Shiah

Roberts

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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-Contractions in whole skeletal muscle during hypoxia are known to generate reactive oxygen species (ROS); however, identification of real-time ROS formation within isolated single skeletal muscle fibers has been challenging. Consequently, there is no convincing evidence showing increased ROS production in intact contracting fibers under low PO2 conditions. Therefore, we hypothesized that intracellular ROS generation in single contracting skeletal myofibers increases during low PO2 compared with a value approximating normal resting PO2. Dihydrofluorescein was loaded into single frog (Xenopus) fibers, and fluorescence was used to monitor ROS using confocal microscopy. Myofibers were exposed to two maximal tetanic contractile periods (1 contraction/3 s for 2 min, separated by a 60-min rest period), each consisting of one of the following treatments: high PO2 (30 Torr), low PO2 (3-5 Torr), high PO2 with ebselen (antioxidant), or low PO2 with ebselen. Ebselen (10 M) was administered before the designated contractile period. ROS formation during low PO2 treatment was greater than during high PO2 treatment, and ebselen decreased ROS generation in both low-and high-PO2 conditions (P Ͻ 0.05). ROS accumulated at a faster rate in low vs. high PO2. Force was reduced Ͼ30% for each condition except low PO2 with ebselen, which only decreased ϳ15%. We concluded that single myofibers under low PO2 conditions develop accelerated and more oxidative stress than at PO2 ϭ 30 Torr (normal human resting PO2). Ebselen decreases ROS formation in both low and high PO2, but only mitigates skeletal muscle fatigue during reduced PO2 conditions. hypoxia; confocal; reactive oxygen species; ebselen; myofiber REACTIVE OXYGEN SPECIES (ROS) play important roles in biological systems (1,44,46,47,49,50). ROS have been documented as a general response to ischemia-reperfusion injury (26, 43), muscle stimulation (29), and heat stress (44). Excessive ROS disrupt nearly all physiological systems (1,44,46,47,49,50). However, the underlying mechanism of ROS formation in hypoxic skeletal muscle has not been fully elucidated. Moreover, there has been little investigation of ROS generation within single skeletal muscle fibers under low PO 2 conditions using real-time measurements, which eliminates some of the problems associated with these measurements that have been made in whole animal or whole muscle preparations (46). Previous research suggests that in human skeletal muscle, intracellular PO 2 drops from ϳ30 Torr at rest to 3-5 Torr during exercise (40). Thus, it is of interest to investigate intracellular ROS formation during these conditions of low PO 2 in single contracting myocytes.Hypoxia causes a significant accumulation of reducing agents in the mitochondria, such as NADH and FADH 2 . Abrupt exposure to O 2 can promote immediate formation of superoxide anion (O 2 ·Ϫ ) in the mitochondrial electron transport chain (2, 37), thus initiating oxidative stress. Moreover, substantial data point to intracellular ROS formation in cardiac tissue during hypo...

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The Radical Trap 5,5-Dimethyl-1-PyrrolineN-Oxide Exerts Dose-Dependent Protection against Myocardial Ischemia-Reperfusion Injury through Preservation of Mitochondrial Electron Transport

Cited by 47 publications

References 46 publications

The role of mitochondria in cardiac development and protection

The role of mitochondria in cardiac development and protection

Methods for Detection of Mitochondrial and Cellular Reactive Oxygen Species

Low Po₂conditions induce reactive oxygen species formation during contractions in single skeletal muscle fibers

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The Radical Trap 5,5-Dimethyl-1-PyrrolineN-Oxide Exerts Dose-Dependent Protection against Myocardial Ischemia-Reperfusion Injury through Preservation of Mitochondrial Electron Transport

Cited by 47 publications

References 46 publications

The role of mitochondria in cardiac development and protection

The role of mitochondria in cardiac development and protection

Methods for Detection of Mitochondrial and Cellular Reactive Oxygen Species

Low Po2conditions induce reactive oxygen species formation during contractions in single skeletal muscle fibers

Contact Info

Product

Resources

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Low Po₂conditions induce reactive oxygen species formation during contractions in single skeletal muscle fibers