Dynamic, in vivo, real-time detection of retinal oxidative status in a model of elevated intraocular pressure using a novel, reversibly responsive, profluorescent nitroxide probe

Rayner, Cassie L.; Gole, Glen A.; Bottle, Steven E.; Barnett, Nigel L.

doi:10.1016/j.exer.2014.10.013

Cited by 20 publications

(14 citation statements)

References 85 publications

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“…IF on isolated cells was performed as described previously [32]. For retina samples, IF staining was performed on 10 mm frozen sections without Hoechst incubation, as described previously [35].…”

Section: Ifmentioning

confidence: 99%

Rats with a missense mutation in Atm display neuroinflammation and neurodegeneration subsequent to accumulation of cytosolic DNA following unrepaired DNA damage

Quek

Luff

Cheung

et al. 2016

Journal of Leukocyte Biology

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Mutations in the ataxia-telangiectasia (A-T)-mutated () gene give rise to the human genetic disorder A-T, characterized by immunodeficiency, cancer predisposition, and neurodegeneration. Whereas a series of animal models recapitulate much of the A-T phenotype, they fail to present with ataxia or neurodegeneration. We describe here the generation of an missense mutant [amino acid change of leucine (L) to proline (P) at position 2262 (L2262P)] rat by intracytoplasmic injection (ICSI) of mutant sperm into oocytes.-mutant rats ( ) expressed low levels of ATM protein, suggesting a destabilizing effect of the mutation, and had a significantly reduced lifespan compared with Whereas these rats did not show cerebellar atrophy, they succumbed to hind-limb paralysis (45%), and the remainder developed tumors. Closer examination revealed the presence of both dsDNA and ssDNA in the cytoplasm of cells in the hippocampus, cerebellum, and spinal cord of rats. Significantly increased levels of IFN-β and IL-1β in all 3 tissues were indicative of DNA damage induction of the type 1 IFN response. This was further supported by NF-κB activation, as evidenced by p65 phosphorylation (P65) and translocation to the nucleus in the spinal cord and parahippocampus. Other evidence of neuroinflammation in the brain and spinal cord was the loss of motor neurons and the presence of increased activation of microglia. These data provide support for a proinflammatory phenotype that is manifested in the mutant rat as hind-limb paralysis. This mutant represents a useful model to investigate the importance of neuroinflammation in A-T.

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Section: Ifmentioning

confidence: 99%

Rats with a missense mutation in Atm display neuroinflammation and neurodegeneration subsequent to accumulation of cytosolic DNA following unrepaired DNA damage

Quek

Luff

Cheung

et al. 2016

Journal of Leukocyte Biology

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“…Upon removal of the paramagnetic nitroxide moiety from a PFN molecule, through redox chemistry or by the trapping of a radical, the fluorescence signal of the fluorophore is revealed. PFNs have been applied as probes in numerous contexts, including detecting reactive oxygen species in biological systems, identifying radical reaction intermediates,, evaluating the oxidative capacity of pollution and monitoring and imaging polymer degradation , …”

Section: Introductionmentioning

confidence: 99%

BODIPY‐Based Profluorescent Probes Containing Meso‐ and β‐Substituted Isoindoline Nitroxides

et al. 2017

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BODIPY is a highly versatile fluorophore for biological imaging with a tunable fluorescence emission (500–800 nm) that overlaps the optically transparent window for tissue (600–1300 nm). Herein, we describe the synthesis of optically distinct BODIPY‐based profluorescent probes bearing meso‐ and β‐substituted isoindoline nitroxides and their corresponding methoxyamine derivatives. These profluorescent nitroxide probes possess strongly suppressed fluorescence, which can be revealed upon reduction or reaction with other radicals. Examination of the pentafluorophenylhydrazine reduction of the prepared probes by using tandem electron paramagnetic resonance (EPR) and fluorescence spectroscopy demonstrated that the asymmetric bis‐β‐substituted probe 9 (λem = 603 nm) was reduced the fastest; however, the greatest difference in fluorescence emission between the nitroxide and its reduced hydroxylamine analogue was observed for probe 7 (λem = 570 nm). The significant difference in fluorescence output between the nitroxides and their corresponding diamagnetic derivatives makes these probes ideal tools for imaging reactive oxygen species in biological systems.

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“…[10,11] To enable fluorescent detection, the nitroxide moiety can be covalently tethered to af luorophore of choice through as uitable linker.T he nitroxyl free radical will quench the fluorophores fluorescence, [12] which can be restored either [23] n.a. 460/4953 -fold increase HeLa cells, isolatedm itochondria -N ADH, rotenone, succinate and malonate ME-TRN [27] O 2 C À 556/590N /A Albino Spraguee Dawley rats -acute retinal ischaemia-reperfusion -lutein ORCAFluor [28] Ascorbate and GSH 640/7302 -to3. 5 [36] GSH 488/5144 -fold decrease HeLa -H 2 O 2 , a-lipoic acid and NEM Chalcogenoxides Cy-PSe [37] ONOO À 758/7752 3.3-fold increase RAW264.7 -SIN-1, GST,L PS, IFN-g,P MA, NOC-5 and TEMPO MPh-Se-BOD [38] -OCl 460/475-650 5f old increase RAW264.7 -PMA, Taurine, Xanth./Xanth.…”

Section: Nitroxide-based Probesmentioning

confidence: 99%

“…465/480 490 (970) TP / 511 70-fold increase 7-fold increase CHO cells -H 2 O 2 ,C ellROX deep red Fluorescein-TEMPO [22] O 2 C À and NOC 492/5142 .2-to 2.7-fold increase hTERT-immortalized fibroblasts -2 DG and rotenone MitoRP [23] n.a. 460/4953 -fold increase HeLa cells, isolatedm itochondria -N ADH, rotenone, succinate and malonate ME-TRN [27] O 2 C À 556/590N /A Albino Spraguee Dawley rats -acute retinal ischaemia-reperfusion -lutein ORCAFluor [28] Ascorbate and GSH 640/7302 -to3.5-fold increase…”

Section: Hela Cells-ascorbatementioning

confidence: 99%

Reversible Fluorescent Probes for Biological Redox States

2015

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The redox chemistry of the cell is key to its function and health, and the development of chemical tools to study redox biology is important. While fluxes in oxidative state are essential for healthy cell function, a chronically elevated oxidative capacity is linked to disease. It is therefore essential that probes of biological redox states distinguish between these two conditions by the reversible sensing of changes over time. In this review, we discuss the current progress towards such probes, and identify key directions for future research in this nascent field of vital biological interest.

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Dynamic, in vivo, real-time detection of retinal oxidative status in a model of elevated intraocular pressure using a novel, reversibly responsive, profluorescent nitroxide probe

Cited by 20 publications

References 85 publications

Rats with a missense mutation in Atm display neuroinflammation and neurodegeneration subsequent to accumulation of cytosolic DNA following unrepaired DNA damage

Rats with a missense mutation in Atm display neuroinflammation and neurodegeneration subsequent to accumulation of cytosolic DNA following unrepaired DNA damage

BODIPY‐Based Profluorescent Probes Containing Meso‐ and β‐Substituted Isoindoline Nitroxides

Reversible Fluorescent Probes for Biological Redox States

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