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Molecular & Cellular Proteomics : MCP Jul 2008Lipofuscin accumulates with age in the retinal pigment epithelium (RPE) in discrete granular organelles and may contribute to age-related macular degeneration. Because...
Lipofuscin accumulates with age in the retinal pigment epithelium (RPE) in discrete granular organelles and may contribute to age-related macular degeneration. Because previous studies suggest that lipofuscin contains protein that may impact pathogenic mechanisms, we pursued proteomics analysis of lipofuscin. The composition of RPE lipofuscin and its mechanisms of pathogenesis are poorly understood in part because of the heterogeneity of isolated preparations. We purified RPE lipofuscin granules by treatment with proteinase K or SDS and showed by light, confocal, and transmission electron microscopy that the purified granules are free of extragranular material and associated membranes. Crude and purified lipofuscin preparations were quantitatively compared by (i) LC MS/MS proteomics analyses, (ii) immunoanalyses of oxidative protein modifications, (iii) amino acid analysis, (iv) HPLC of bisretinoids, and (v) assaying phototoxicity to RPE cells. From crude lipofuscin preparations 186 proteins were identified, many of which appeared to be modified. In contrast, very little protein ( approximately 2% (w/w) by amino acid analysis) and no identifiable protein were found in the purified granules, which retained full phototoxicity to cultured RPE cells. Our analyses showed that granules in purified and crude lipofuscin preparations exhibit no statistically significant differences in diameter or circularity or in the content of the bisretinoids A2E, isoA2E, and all-trans-retinal dimer-phosphatidylethanolamine. The finding that the purified granules contain minimal protein yet retain phototoxic activity suggests that RPE lipofuscin pathogenesis is largely independent of associated protein. The purified granules also exhibited oxidative protein modifications, including nitrotyrosine generated from reactive nitrogen oxide species and carboxyethylpyrrole and iso[4]levuglandin E(2) adducts generated from reactive lipid fragments. This finding is consistent with previous studies demonstrating RPE lipofuscin to be a potent generator of reactive oxygen species and supports the hypothesis that such species, including reactive fragments from lipids and retinoids, contribute to the mechanisms of RPE lipofuscin pathogenesis.
Topics: Aged; Amino Acid Sequence; Cell Survival; Eye Proteins; Humans; Light; Lipofuscin; Oxidation-Reduction; Pigment Epithelium of Eye; Protein Processing, Post-Translational; Proteomics; Retinoids
PubMed: 18436525
DOI: 10.1074/mcp.M700525-MCP200 -
Journal of the American Academy of... Sep 2014
Topics: Anti-Bacterial Agents; Ciprofloxacin; Dermatitis, Phototoxic; Disease Progression; Female; Humans; Stevens-Johnson Syndrome; Young Adult
PubMed: 25128136
DOI: 10.1016/j.jaad.2014.02.033 -
Organic & Biomolecular Chemistry Mar 2015We report the synthesis of four new cationic dipolar push–pull dyes, together with an evaluation of their photophysical and photobiological characteristics pertinent...
We report the synthesis of four new cationic dipolar push–pull dyes, together with an evaluation of their photophysical and photobiological characteristics pertinent to imaging membranes by fluorescence and second harmonic generation (SHG). All four dyes consist of an N,N-diethylaniline electron-donor conjugated to a pyridinium electron-acceptor via a thiophene bridge, with either vinylene (–CH=CH–) or ethynylene (–C≡C–) linking groups, and with either singly-charged or doubly-charged pyridinium terminals. The absorption and fluorescence behavior of these dyes were compared to a commercially available fluorescent membrane stain, the styryl dye FM4-64. The hyperpolarizabilities of all dyes were compared using hyper-Rayleigh scattering at 800 nm. Cellular uptake, localization, toxicity and phototoxicity were evaluated using tissue cell cultures (HeLa, SK-OV-3 and MDA-231). Replacing the central alkene bridge of FM4-64 with a thiophene does not substantially change the absorption, fluorescence or hyperpolarizability, whereas changing the vinylene-links to ethynylenes shifts the absorption and fluorescence to shorter wavelengths, and reduces the hyperpolarizability by about a factor of two. SHG and fluorescence imaging experiments in live cells showed that the doubly-charged thiophene dyes localize in plasma membranes, and exhibit lower internalization rates compared to FM4-64, resulting in less signal from the cell cytosol. At a typical imaging concentration of 1 μM, the doubly-charged dyes showed no significant light or dark toxicity, whereas the singly-charged dyes are phototoxic even at 0.5 μM. The doubly-charged dyes showed phototoxicity at concentrations greater than 10 μM, although they do not generate singlet oxygen, indicating that the phototoxicity is type I rather than type II. The doubly-charged thiophene dyes are more effective than FM4-64 as SHG dyes for live cells.
Topics: Cell Line, Tumor; Cell Membrane; Cell Survival; Coloring Agents; Humans; Models, Molecular; Nonlinear Dynamics; Optical Phenomena; Spectrometry, Fluorescence; Static Electricity; Thiophenes; Unilamellar Liposomes
PubMed: 25703541
DOI: 10.1039/c4ob02507e -
Skin Pharmacology and Physiology 2017One of the most important dermatologic side effects of doxycycline is photosensitivity. As doxycycline is important for malaria prophylaxis and malaria is mainly spread... (Review)
Review
BACKGROUND
One of the most important dermatologic side effects of doxycycline is photosensitivity. As doxycycline is important for malaria prophylaxis and malaria is mainly spread in countries with high sun radiation, special attention should be paid to this adverse effect. While there are many publications on the phototoxicity of tetracyclines in general, only a few exist focusing on doxycycline. The objective of this systematic review was to summarize all available reports on clinical manifestations, influencing factors like UV dose or dose of medication, and the possibilities of prevention by sun protection.
METHODS
This review is based on a systematic search in PubMed for articles in English and German and a manual search between 1990 and 2015.
RESULTS
The number of publications is low. Clinical symptoms vary from light sunburn-like sensation (burning, erythema) to large-area photodermatitis. Also, onycholysis is possible. The triggering UV spectrum seems to consist mainly of UVA1 (340-400 nm), so UV-protective products should be used that cover this range. Travelers to tropical countries taking doxycycline for malaria prophylaxis need thorough medical counseling to avoid possibly severe phototoxic reactions.
CONCLUSION
Evidence base must be improved for giving advice on appropriate prevention measures to travelers taking doxycycline and having a risk of significant sun exposure.
Topics: Anti-Bacterial Agents; Doxycycline; Humans; Malaria; Onycholysis; Photosensitivity Disorders; Sunlight; Ultraviolet Rays
PubMed: 28291967
DOI: 10.1159/000458761 -
The New Phytologist Nov 1992Sunlight provides the energy required for all biochemical, physiological and developmental processes necessary for plant growth, reproduction and survival. The role of... (Review)
Review
Sunlight provides the energy required for all biochemical, physiological and developmental processes necessary for plant growth, reproduction and survival. The role of light in photosynthesis and photomorphogenesis has been appreciated for some time; however, the role of light in plant defence is a comparatively recent realization. Between 75-100 photosensitizers or phototoxins, molecules that become toxic in the presence of light, have been extracted from higher plant tissues. These biologically-active compounds have diverse biosynthetic origins and belong to at least 15 different phytochemical classes (i.e. acetophenones, acetylenes, benzophenanthrenes, β-carbolines, coumarins, extended quinones, furanochromones, furanocoumarins, furanoquinolines, isoquinolines, lignans, pterocarpans, quinolines, sesquiterpenes and thiophenes). Of more than 100 angiosperm families assayed, phototoxins and/or phototoxic activity have been reported in c. 40 families representing 32 orders and 8 subclasses of the Magnoliophyta. Most of these allelochemicals are acute toxins with little organism-specificity. As such, they are effective biocides capable of killing a wide-range of potentially harmful organisms including: viruses, pathogenic bacteria and fungi, nematodes and herbivorous insects, as well as competing plant species. This review focuses on the phytochemistry, taxonomic occurrence and toxicological consequences of phototoxic metabolites in flowering plants. The available information suggests that phototoxic phytochemicals: (i) are broad-spectrum allelochemicals capable of protecting plants against a variety of detrimental organisms in nature, (ii) represent a successful defensive strategy in both primitive and advanced plant taxa, and (iii) may be an effective defence under a variety of photoenvironmental conditions. CONTENTS Summary 401 I. Introduction 401 II. Chemistry/biochemistry of plant photosensitizers 402 III. Botanical distribution of photosensitizers 403 IV. Toxicology 405 V. Biological activity/defensive role of photosensitizers 408 VI. Concluding remarks 413 References 415.
PubMed: 33874213
DOI: 10.1111/j.1469-8137.1992.tb00068.x -
Applied Microbiology and Biotechnology Jun 2022While phototoxicity can be a useful therapeutic modality not only for eliminating malignant cells but also in treating fungal infections, mycologists aiming to observe... (Review)
Review
While phototoxicity can be a useful therapeutic modality not only for eliminating malignant cells but also in treating fungal infections, mycologists aiming to observe morphological changes or molecular events in fungi, especially when long observation periods or high light fluxes are warranted, encounter problems owed to altered regulatory pathways or even cell death caused by various photosensing mechanisms. Consequently, the ever expanding repertoire of visible fluorescent protein toolboxes and high-resolution microscopy methods designed to investigate fungi in vitro and in vivo need to comply with an additional requirement: to decrease the unwanted side effects of illumination. In addition to optimizing exposure, an obvious solution is red-shifted illumination, which, however, does not come without compromises. This review summarizes the interactions of fungi with light and the various molecular biology and technology approaches developed for exploring their functions on the molecular, cellular, and in vivo microscopic levels, and outlines the progress towards reducing phototoxicity through applying far-red and near-infrared light. KEY POINTS: • Fungal biological processes alter upon illumination, also under the microscope • Red shifted fluorescent protein toolboxes decrease interference by illumination • Innovations like two-photon, lightsheet, and near IR microscopy reduce phototoxicity.
Topics: Coloring Agents; Fungi; Light; Microscopy, Fluorescence; Photons
PubMed: 35599256
DOI: 10.1007/s00253-022-11967-2 -
Free Radical Biology & Medicine Sep 2019Phototoxic effects of 6,8 dihalogenated quinolones confers to this type of molecules a potential property as photochemotherapeutic agents. Two photodehalogenation...
Phototoxic effects of 6,8 dihalogenated quinolones confers to this type of molecules a potential property as photochemotherapeutic agents. Two photodehalogenation processes seem to be involved in the remarkable photoinduced cellular damage. In this context, a new 6,8 dihalogenated quinolone 1 (1-methyl-6,8-difluoro-4-oxo-7-aminodimethyl-1,4-dihydroquinoline-3-carboxylic acid) was synthetized looking for improving the phototoxic properties of fluoroquinolones (FQ) and to determine the role of the photodegradation pathways in the FQ phototoxicity. With this purpose, fluorescence emissions, laser flash photolysis experiments and photodegradation studies were performed with compound 1 using 1-ethyl-6,8-difluoro-4-oxo-7-aminodimethyl-1,4-dihidroquinoline-3-carboxylic acid (2) and lomefloxacin (LFX) as reference compounds. The shortening of alkyl chain of the N(1) of the quinolone ring revealed a lifetime increase of the reactive aryl cation generated from photolysis of the three FQ and a significant reduction of the FQ photodegradation quantum yield. The fact that these differences were smaller when the same study was done using a hydrogen donor solvent (ethanol-aqueous buffer, 50/50 v/v) evidenced the highest ability of the reactive intermediate arising from 1 to produce intermolecular alkylations. These results were correlated with in vitro 3T3 NRU phototoxicity test. Thus, when Photo-Irritation-Factor (PIF) was determined for 1, 2 and LFX using cytotoxicity profiles of BALB/c 3T3 fibroblasts treated with each compound in the presence and absence of UVA light, a PIF more higher than 30 was obtained for 1 while the values for 2 and LFX were only higher than 8 and 10, respectively. Thereby, the present study illustrates an approach to modulate the photosensitizing properties of FQ with the purpose to improve the chemotherapeutic properties of antitumor quinolones. Moreover, the results obtained in this study also evidence that the key pathway responsible for the phototoxic properties associated with dihalogenated quinolones is the aryl cation generation.
Topics: 3T3 Cells; Animals; Antineoplastic Agents; Dermatitis, Phototoxic; Drug Design; Fluoroquinolones; Halogens; Lasers; Methane; Mice; Mice, Inbred BALB C; Microscopy, Confocal; Photochemistry; Quinolones; Singlet Oxygen
PubMed: 31195085
DOI: 10.1016/j.freeradbiomed.2019.06.010 -
Romanian Journal of Morphology and... 2014Vision is based on the sensitivity of the eye to visible rays of the solar spectrum, which allows the recording and transfer of visual information by photoelectric... (Review)
Review
Vision is based on the sensitivity of the eye to visible rays of the solar spectrum, which allows the recording and transfer of visual information by photoelectric reaction. Any electromagnetic radiation, if sufficiently intense, may cause damages in living tissues. In a changing environment, the aim of this paper is to point out the impact of light radiation on ocular cells, with its phototoxicity potential on eye tissues. In fact, faced with light and oxygen, the eye behaves like an ephemeral aggregate of unstable molecules, like a temporary crystallization threatened with entropia.
Topics: Cornea; Dermatitis, Phototoxic; Electromagnetic Radiation; Eye; Humans; Lens, Crystalline; Light; Ultraviolet Rays; Vision, Ocular
PubMed: 24969972
DOI: No ID Found -
Pharmaceutics Oct 2022The study of phthalocyanines, known photosensitizers, for biomedical applications has been of high research interest for several decades. Of specific interest,...
The study of phthalocyanines, known photosensitizers, for biomedical applications has been of high research interest for several decades. Of specific interest, nanophotosensitizers are crystalline aluminum phthalocyanine nanoparticles (AlPc NPs). In crystalline form, they are water-insoluble and atoxic, but upon contact with tumors, immune cells, or pathogenic microflora, they change their spectroscopic properties (acquire the ability to fluoresce and become phototoxic), which makes them upcoming agents for selective phototheranostics. Aqueous colloids of crystalline AlPc NPs with a hydrodynamic size of 104 ± 54 nm were obtained using ultrasonic dispersal and centrifugation. Intracellular accumulation and localization of AlPc were studied on HeLa and THP-1 cell cultures and macrophages (M0, M1, M2) by fluorescence microscopy. Crystallinity was assessed by XRD spectroscopy. Time-resolved spectroscopy was used to obtain characteristic fluorescence kinetics of AlPc NPs upon interaction with cell cultures. The photodynamic efficiency and fluorescence quantum yield of AlPc NPs in HeLa and THP-1 cells were evaluated. After entering the cells, AlPc NPs localized in lysosomes and fluorescence corresponding to individual AlPc molecules were observed, as well as destruction of lysosomes and a rapid decrease in fluorescence intensity during photodynamic action. The photodynamic efficiency of AlPc NPs in THP-1 cells was almost 1.8-fold that of the molecular form of AlPc (Photosens). A new mechanism for the occurrence of fluorescence and phototoxicity of AlPc NPs in interaction with cells is proposed.
PubMed: 36297557
DOI: 10.3390/pharmaceutics14102122 -
International Journal of Molecular... May 2023The widespread role of titanium (IV) oxide (TiO) in many industries makes this substance of broad scientific interest. TiO can act as both a photoprotector and... (Review)
Review
The widespread role of titanium (IV) oxide (TiO) in many industries makes this substance of broad scientific interest. TiO can act as both a photoprotector and photocatalyst, and the potential for its role in both applications increases when present in nanometer-sized crystals. Its sunlight-scattering properties are used extensively in sunscreens. Furthermore, attempts have been made to incorporate TiO into dermal formulations of photolabile drugs. However, the propensity to generate reactive oxygen species (ROS) rendering this material potentially cytotoxic limits its role. Therefore, modifications of TiO nanoparticles (e.g., its polymorphic form, size, shape, and surface modifications) are used in an effort to reduce its photocatalytic effects. This review provides an overview of the potential risks arising from and opportunities presented by the use of TiO in skin care formulations.
Topics: Humans; Titanium; Oxides; Dermatitis, Phototoxic; Nanoparticles
PubMed: 37175865
DOI: 10.3390/ijms24098159