Unraveling the Biological Roles of Reactive Oxygen Species

Murphy, Michael P.; Holmgren, Arne; Larsson, Nils‐Göran; Halliwell, Barry; Chang, Christopher J.; Kalyanaraman, Balaraman; Rhee, Sue Goo; Thornalley, Paul J.; Partridge, Linda; Gems, David; Nyström, Thomas; Belousov, Vsevolod V.; Schumacker, Paul T.; Winterbourn, Christine C.

doi:10.1016/j.cmet.2011.03.010

Cited by 710 publications

(563 citation statements)

References 43 publications

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“…By contrast, DCFH reacts best with both ONOO -and • OH ( Figure 2C) and to a lesser extent with -OCl and O 2 •-, but not H 2 O 2 , as shown in Figure 2C. This lack of reactivity to H 2 O 2 is consistent with some literature [10], but contrasts other reports that infer the detection of H 2 O 2 using this probe [9]. However, DCFH is able to detect other ROS such as • OH produced from H 2 O 2 in vivo, and also H 2 O 2 in the presence of peroxidases [11].…”

Section: Ros Characterisation Of Probessupporting

confidence: 89%

“…•-production [9]. An aryl boronate probe reported by Chang et al [12], peroxyfluor-1 (PF1), reacts with both H 2 O 2 and ONOO -; but not • OH, O 2…”

Section: Introductionmentioning

confidence: 99%

“…DCFH is a fluorescein-based nonspecific probe that reportedly reacts with H 2 O 2 [9] and other ROS, particularly hydroxyl radicals ( • OH) and peroxynitrite (ONOO -) [10]. This probe has some disadvantages, since it requires the concomitant presence of peroxidases to react with H 2 O 2 [11], can undergo autoxidation and is known to catalyse O 2…”

Section: Introductionmentioning

confidence: 99%

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Boronate probes for the detection of hydrogen peroxide release from human spermatozoa

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Connaughton

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Free Radical Biology and Medicine

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Section: Ros Characterisation Of Probessupporting

confidence: 89%

“…•-production [9]. An aryl boronate probe reported by Chang et al [12], peroxyfluor-1 (PF1), reacts with both H 2 O 2 and ONOO -; but not • OH, O 2…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Boronate probes for the detection of hydrogen peroxide release from human spermatozoa

Purdey

Connaughton

Whiting

et al. 2015

Free Radical Biology and Medicine

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“…To really advance this field of research sport science needs to collaborate with redox biologists and combine the skills of both sets of scientists. [159] they work in distinct ways and importantly they do not solely regulate ROS. This is important because just because one is using an antioxidant it is not to say that it is acting as an antioxidant, which is especially important for nutritional antioxidants.…”

Section: Beta-alanine More Recently Muscle Concentrations Of the DImentioning

confidence: 99%

New strategies in sport nutrition to increase exercise performance

Hamilton

Philp

et al. 2016

Free Radical Biology and Medicine

178

118

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Despite over 50 years of research, the field of sports nutrition continues to grow at a rapid rate. Whilst the traditional research focus was one that centred on strategies to maximize competition performance, emerging data in the last decade has demonstrated how both macronutrient and micronutrient availability can play a prominent role in regulating those cell signalling pathways that modulate skeletal muscle adaptations to endurance and resistance training. Nonetheless, in the context of exercise performance, it is clear that carbohydrate (but not fat) still remains king and that carefully chosen ergogenic aids (e.g. caffeine, creatine, sodium bicarbonate, beta-alanine, nitrates) can all promote performance in the correct exercise setting. In relation to exercise training, however, it is now thought that strategic periods of reduced carbohydrate and elevated dietary protein intake may enhance training adaptations whereas high carbohydrate availability and antioxidant supplementation may actually attenuate training adaptation. Emerging evidence also suggests that vitamin D may play a regulatory role in muscle regeneration and subsequent hypertrophy following damaging forms of exercise. Finally, novel compounds (albeit largely examined in rodent models) such as epicatechins, nicotinamide riboside, resveratrol, β-hydroxy β-methylbutyrate, phosphatidic acid and ursolic acid may also promote or attenuate skeletal muscle adaptations to endurance and strength training. When taken together, it is clear that sports nutrition is very much at the heart of the Olympic motto, Citius, Altius, Fortius (faster, higher, stronger).

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“…Furthermore, there is growing evidence that different ROS have different effects, and that these effects are location and concentration dependent (35). Therefore, a range of mitochondria---targeted sensors have been reported ( Figure 7).…”

Section: Mitochondria---targeted Sensorsmentioning

confidence: 99%

Targeting Mitochondria with Small Molecules: The Preparation of MitoB and MitoP as Exomarkers of Mitochondrial Hydrogen Peroxide

Cairns

McQuaker

Murphy

et al. 2015

Methods in Molecular Biology

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Small molecules can be physicochemically targeted to mitochondria using the lipophilic alkyltriphenylphosphonium (TPP) group. Once in the mitochondria the TPP---conjugate can detect or influence processes within the mitochondrial matrix directly. Alternatively, the conjugate can behave as a prodrug, which is activated by release from the TPP group either using an internal or external instruction. Small molecules can be designed that can be used in any cell line, tissue or whole organism, allow temporal control, and be applied in a reversible dose---dependent fashion. An example is the detection and quantification of hydrogen peroxide in mitochondria of whole living organisms by MitoB. Hydrogen peroxide produced within the mitochondrial matrix is involved in signalling and implicated in the oxidative damage associated with aging and a wide range of age---associated conditions including cardiovascular disease, neurodegeneration and cancer. MitoB accumulates in mitochondria and is converted into the exomarker, MitoP, by hydrogen peroxide in the mitochondrial matrix. The hydrogen peroxide concentration is determined from the ratio of MitoP to MitoB after a period of incubation, and this ratio is determined by mass spectrometry using d15---MitoP and d15---MitoB as standard. 2Here we describe the synthesis of MitoB and MitoP and the deuterated standards necessary for this method of quantification.1. Introduction Mitochondria---targeted drugs and prodrugsSmall molecule drugs are vital to medicine (1). They can often be administered orally, and produce rapid dose---dependent effects. Similarly, small molecules are useful tools to the molecular biologist seeking to elucidate biological processes. A key advantage to small molecules is that in theory they can be used in any cell line, tissue, organ or organism. Their use does not require the manipulation of proteins and gene expression through mutation and RNA---dependent gene silencing, so they can be applied to native tissues and organisms. Furthermore, a small molecule that is useful for the study of a biological process can often be a lead compound for drug discovery, and vice versa.Mitochondria play a central role in metabolism, supplying most of the ATP used by cells, and also are key to signalling, homeostasis, and the events leading up to apoptosis and necrosis (2,3). Mitochondrial dysfunction contributes to almost every age---associated disease including cardiovascular diseases, neurodegeneration and cancer (2), and is implicated in the process of aging itself (4,5).Drugs can act on targets in the mitochondria without having an independent mechanism for their accumulation there. However, efficacy would be increased and side---effects decreased if the concentration of a drug is elevated near its site of action.For this reason, it is desirable to have a mechanism of targeting small molecules to the mitochondria, and in particular the mitochondrial matrix where much of 3 metabolism is sited. Fortunately, there are a variety of approaches for the delivery of molecular...

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Unraveling the Biological Roles of Reactive Oxygen Species

Cited by 710 publications

References 43 publications

Boronate probes for the detection of hydrogen peroxide release from human spermatozoa

Boronate probes for the detection of hydrogen peroxide release from human spermatozoa

New strategies in sport nutrition to increase exercise performance

Targeting Mitochondria with Small Molecules: The Preparation of MitoB and MitoP as Exomarkers of Mitochondrial Hydrogen Peroxide

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