A Unique Approach to Development of Near-Infrared Fluorescent Sensors for in Vivo Imaging

Journal of the American Chemical Society, Год журнала: 2012, Номер 134(32), С. 13510 - 13523

Опубликована: Июль 20, 2012

Near-infrared (NIR) fluorescent sensors have emerged as promising molecular tools for imaging biomolecules in living systems. However, NIR are very challenging to be developed. Herein, we describe the discovery of a new class dyes represented by 1a/1c/1e, which superior traditional 7-hydroxycoumarin and fluorescein with both absorption emission region while retaining an optically tunable hydroxyl group. Quantum chemical calculations B3LYP exchange functional employing 6-31G(d) basis sets provide insights into optical property distinctions between 1a/1c/1e their alkoxy derivatives. The unique properties type can exploited useful strategy development sensors. Employing this strategy, two different types sensors, NIR-H2O2 NIR-thiol, H2O2 thiols, respectively, were constructed. These novel respond or thiols large turn-on fluorescence signal upon excitation region. Furthermore, NIR-thiol capable endogenously produced not only cells but also mice, demonstrating value sensor design strategy. presented herein may open up opportunities based on functionalized reactive sites biological applications animals.

Язык: Английский

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Reducing oxidative/nitrosative stress: a newly-discovered genre for melatonin

Critical Reviews in Biochemistry and Molecular Biology, Год журнала: 2009, Номер 44(4), С. 175 - 200

Опубликована: Июль 6, 2009

The discovery of melatonin and its derivatives as antioxidants has stimulated a very large number studies which have, virtually uniformly, documented the ability these molecules to detoxify harmful reactants reduce molecular damage. These observations have clear clinical implications given that numerous age-related diseases in humans an important free radical component. Moreover, major theory explain processes aging invokes radicals their causative agents. conditions, coupled with loss organisms age, suggest some aspects may be aggravated by diminished levels advanced age. Another corollary this is administration melatonin, uncommonly low toxicity profile, could theoretically defer progression possibly forestall signs aging. Certainly, research next decade will help define role determining successful While increasing life span not necessarily goal investigative efforts, improving health quality aged should aim research.

Язык: Английский

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Protective effects of melatonin in reducing oxidative stress and in preserving the fluidity of biological membranes: a review

Journal of Pineal Research, Год журнала: 2014, Номер 56(3), С. 225 - 237

Опубликована: Фев. 26, 2014

Abstract Free radicals generated within subcellular compartments damage macromolecules which lead to severe structural changes and functional alterations of cellular organelles. A manifestation free radical injury biological membranes is the process lipid peroxidation, an autooxidative chain reaction in polyunsaturated fatty acids membrane are substrate. There considerable evidence that tends reduce fluidity. However, adequate levels fluidity essential for proper functioning membranes. Thus, there interest antioxidant molecules able stabilize because their protective effects against peroxidation. Melatonin indoleamine modulates a wide variety endocrine, neural immune functions. Over last two decades, intensive research has proven this molecule, as well its metabolites, possess substantial activity. In addition ability scavenge several reactive oxygen nitrogen species, melatonin increases activity glutathione redox enzymes, is, peroxidase reductase, other enzymes. These beneficial more significant small molecular size amphipathic behaviour, facilitates ease penetration into every compartment. present work, we review current information related maintaining attack, further, discuss implications ageing disease.

Язык: Английский

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Melatonin and Reproduction Revisited

Biology of Reproduction, Год журнала: 2009, Номер 81(3), С. 445 - 456

Опубликована: Май 14, 2009

This brief review summarizes new findings related to the reported beneficial effects of melatonin on reproductive physiology beyond its now well-known role in determining sexual status both long-day and short-day seasonally breeding mammals. Of particular note are those processes that have been shown benefit from ability function reduction oxidative stress. In few species tested, brightly colored secondary characteristics serve as a attractant reportedly enhanced by administration. is potential importance inasmuch brightness ornamental pigmentation also associated with animals highest genetic quality. Free radical damage commonplace during pregnancy has negative mother, placenta, fetus. Because readily pass through easily protects fetus damage, well maternal tissues placenta. Examples conditions which nitrosative stress can be extensive include preeclampsia resulting anoxia or hypoxia followed reflow oxygenated blood into tissue. Given uncommonly low toxicity melatonin, clinical trials warranted document protection against pathophysiological states system free known occur. Finally, improving outcomes vitro fertilization embryo transfer should further tested exploited. The information this article applicability human veterinary medicine.

Язык: Английский

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Antiinflammatory Activity of Melatonin in Central Nervous System

Current Neuropharmacology, Год журнала: 2010, Номер 8(3), С. 228 - 242

Опубликована: Авг. 19, 2010

Melatonin is mainly produced in the mammalian pineal gland during dark phase. Its secretion from has been classically associated with circadian and circanual rhythm regulation. However, melatonin production not confined exclusively to gland, but other tissues including retina, Harderian glands, gut, ovary, testes, bone marrow lens also produce it. Several studies have shown that reduces chronic acute inflammation. The immunomodulatory properties of are well known; it acts on immune system by regulating cytokine immunocompetent cells. Experimental clinical data showing adhesion molecules pro-inflammatory cytokines modifies serum inflammatory parameters. As a consequence, improves course illnesses which an etiology. Moreover, experimental evidence supports its actions as direct indirect antioxidant, scavenging free radicals, stimulating antioxidant enzymes, enhancing activities antioxidants or protecting enzymes oxidative damage. encouraging suggest neuroprotective molecule neurodegenerative disorders where brain damage implicated common link. In this review, authors examine effect several neurological diseases components, dementia, Alzheimer disease, Parkinson multiple sclerosis, stroke, ischemia/reperfusion traumatic CNS injuries (traumatic spinal cord injury).

Язык: Английский

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Melatonin, cardiolipin and mitochondrial bioenergetics in health and disease

Journal of Pineal Research, Год журнала: 2010, Номер 48(4), С. 297 - 310

Опубликована: Апрель 8, 2010

Melatonin is a natural occurring compound with well-known antioxidant properties. ubiquitously distributed and because of its small size amphiphilic nature, it able to reach easily all cellular subcellular compartments. The highest intracellular melatonin concentrations are found in mitochondria, raising the possibility functional significance for this targeting involvement situ mitochondrial activities. Mitochondria, powerhouse cell, considered be most important organelles contribute degenerative processes mainly through respiratory chain dysfunction formation reactive oxygen species, leading damage proteins, lipids DNA. Therefore, protecting mitochondria from oxidative could an effective therapeutic strategy against processes. Many beneficial effects administration may depend on effect physiology. Cardiolipin, phospholipid located at level inner membrane known intimately involved several bioenergetic as well mitochondrial-dependent steps apoptosis. Alterations cardiolipin structure, content acyl composition have been associated multiple tissues physiopathological situations aging. Recently, was reported protect by preventing oxidation explain, least part, molecule physiopathology. In review, we discuss role disease.

Язык: Английский

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Single Fluorescent Probe Responds to H₂O₂, NO, and H₂O₂/NO with Three Different Sets of Fluorescence Signals

Journal of the American Chemical Society, Год журнала: 2011, Номер 134(2), С. 1305 - 1315

Опубликована: Дек. 9, 2011

Hydrogen peroxide (H(2)O(2)) acts as a signaling molecule in wide variety of transduction processes and an oxidative stress marker aging disease. However, excessive H(2)O(2) production is implicated with various diseases. Nitric oxide (NO) serves secondary messenger inducing vascular smooth muscle relaxation. mis-regulation NO associated disorders. To disentangle the complicated inter-relationship between signal pathways, fluorescent reporters that are able to display distinct signals H(2)O(2), NO, H(2)O(2)/NO highly valuable. Herein, we present rational design, synthesis, spectral properties, living cell imaging studies FP-H(2)O(2)-NO, first single-fluorescent molecule, can respond three different sets fluorescence signals. FP-H(2)O(2)-NO senses pattern blue-black-black, black-black-red, black-red-red, respectively. Significantly, have further demonstrated single probe, capable simultaneously monitoring endogenously produced macrophage cells multicolor imaging. We envision will be unique molecular tool investigate interplaying roles complex interaction networks pathways. In addition, this work establishes robust strategy for multiple ROS RNS species (H(2)O(2), H(2)O(2)/NO) using modularity may allow it extended other types biomolecules.

Язык: Английский

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The changing biological roles of melatonin during evolution: from an antioxidant to signals of darkness, sexual selection and fitness

Biological reviews/Biological reviews of the Cambridge Philosophical Society, Год журнала: 2009, Номер 85(3), С. 607 - 623

Опубликована: Дек. 21, 2009

Melatonin is a molecule present in multitude of taxa and may be ubiquitous organisms. It has been found bacteria, unicellular eukaryotes, macroalgae, fungi, plants animals. A primary biological function melatonin primitive organisms antioxidant defence to protect against toxic free radical damage. During evolution, adopted by multicellular perform many other functions. These functions likely include the chemical expression darkness vertebrates, environmental tolerance fungi plants, sexual signaling birds fish, seasonal reproductive regulation photoperiodic mammals, immunomodulation anti-inflammatory activity all vertebrates tested. Moreover, its waning production during aging indicate senescence terms bio-clock Conversely, high levels can serve as signal vitality health. The multiple partially attributed unconventional metabolism which comprised multi-enzymatic, pseudo-enzymatic non-enzymatic pathways. As result, several bioactive metabolites are formed some presumed reported date may, fact, mediated these metabolites. changing roles seem have evolved from an antioxidant.

Язык: Английский

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Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity

Obesity Reviews, Год журнала: 2010, Номер 12(3), С. 167 - 188

Опубликована: Июнь 16, 2010

Summary A worldwide increase in the incidence of obesity indicates unsuccessful battle against this disorder. Obesity and associated health problems urgently require effective strategies treatment. The new discovery that a substantial amount functional brown adipose tissue (BAT) is retained adult humans provides potential target for treatment human obesity. BAT active metabolically disposes extra energy via generation heat through uncoupling oxidative phosphorylation mitochondria. physiology readily regulated by melatonin, which not only increases recruitment adipocytes but also elevates their metabolic activity mammals. It speculated hypertrophic effect activation induced melatonin may likely apply to human. Thus, naturally occurring substance with no reported toxicity, serve as novel approach Conversely, because availability artificial light sources, excessive exposure after darkness onset modern societies should be considered contributory factor at night dramatically reduces endogenous production. In current article, associations BAT, medical implications are discussed.

Язык: Английский

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Melatonin as a powerful bio-antioxidant for reduction of graphene oxide

Journal of Materials Chemistry, Год журнала: 2011, Номер 21(29), С. 10907 - 10907

Опубликована: Янв. 1, 2011

Graphene is usually synthesized through deoxygenation of graphene oxide (GO) by hydrazine as the most common and one strongest reducing agents. But, due to high toxicity hydrazine, it not a promising reductant in large-scale production graphene. Here, for first time, we used melatonin (MLT), powerful antioxidant biocompatible competitor reduction GO suspension. X-ray photoelectron spectroscopy (XPS), current–voltage optical characteristics sheets indicated that efficiency suspensions MLT under heating an alkaline condition 3 h was comparable with obtained similar conditions 30 min. Based on XPS analysis, although amount nitrogen detected surface MLT-reduced higher than hydrazine-reduced ones, smaller C–N bonds were formed former. The assigned π–π adsorption oxidized molecules reduced sheets, which resulted more stability suspension aggregation observed one, also confirmed Raman spectroscopy. A mechanism describing chemical proposed. Our results open up outlook substitution safe, efficient GO, especially bio-applications.

Язык: Английский

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