Lens α-Crystallin and Hypericin: A Photophysical Mechanism Explains Observed Lens Damage†¶

Trevithick-Sutton, Colleen C.; Chin, Khin K.; Contos, Sotiria D.; Foote, Christopher S.

doi:10.1562/0031-8655(2004)080<0444:lcahap>2.0.co;2

Cited by 6 publications

(4 citation statements)

References 40 publications

(41 reference statements)

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“…Anthropogenic sensitizers (dyes, pharmaceuticals, and cosmetics) can serve as oxygen-dependent photodynamic agents and produce singlet oxygen. A number of natural products can also “sensitize” organisms to photochemical damage by oxygen (e.g., chlorophyll, non-iron porphyrins, flavins, polyacetylenes, other plant pigments, and mold toxins). − Hypericin (St. John's Wort, 17 ) represents a natural photooxidation photosensitizer with antitumor and anti-HIV activity; it is sold over the counter and touted to be an antidepressant agent (Scheme ). Other examples include cercosporin ( 18 ), which is a photodynamic mold toxin, and α-terthienyl ( 19 ), which is a photodynamic insecticide from marigolds.…”

Section: Singlet Oxygen Unveiled As a Synthetic And Biological Agentmentioning

confidence: 99%

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Christopher Foote's Discovery of the Role of Singlet Oxygen [¹O₂ (¹Δ_g)] in Photosensitized Oxidation Reactions

2006

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The chemistry of singlet molecular oxygen [1O2 (1Delta g)], its importance in atmospheric, biological, and therapeutic processes, and its use as a reagent in organic synthesis have been of considerable interest. Many aspects of singlet oxygen chemistry have emanated from the work of Christopher S. Foote and co-workers. Singlet oxygen is a historically interesting molecule with an unusual story connected with its discovery. Foote and Wexler conducted experiments in the 1960s where evidence was obtained supporting 1O2 generation via two independent routes: (1) a photochemical reaction (dye-sensitized photooxidation) and (2) a chemical reaction (NaOCl with H2O2). An important factor in the discovery of 1O2 as the critical reaction intermediate in dye-sensitized photooxygenations was Foote's reassessment of the chemical literature of the 1930s, when 1O2 was suggested to be a viable intermediate in dye-sensitized photooxidation reactions. Experiments that used silica gel beads provided evidence for a volatile diffusible oxidant such as 1O2. However, a contemporaneous quarrel surrounded this early work, and the possible existence of solution-phase 1O2 was ignored for over 2 decades. Not long after Foote's initial studies were published in 1964, the idea of singlet oxygen as an intermediate in photooxidation chemistry gained increasing recognition and verification in organic, gas phase, and biological processes. There are many documented impacts that 1O2 has had and continues to have on biology and medicine, for example, photodynamic therapy and plant defenses.

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Section: Singlet Oxygen Unveiled As a Synthetic And Biological Agentmentioning

confidence: 99%

“…tochemical damage by oxygen (e.g., chlorophyll, non-iron porphyrins, flavins, polyacetylenes, other plant pigments, and mold toxins) [90][91][92][93]. Hypericin (St. John's Wort, 17) represents a natural photooxidation photosensitizer with antitumor and anti-HIV activity; it is sold over the counter and touted to be an antidepressant agent (Scheme 13).…”

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confidence: 99%

Christopher Foote's Discovery of the Role of Singlet Oxygen [¹O₂ (¹Δ_g)] in Photosensitized Oxidation Reactions

2006

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“…48 Finally, type II singlet oxygen production followed by oxidation of the protein and/or direct type I interaction of the excited blepharismin with the Trp residues of alpha-crystallin might be the cause of a blepharismin-sensitized photooxidation of Trp. 11,12,49, 50 In the following section (Transient absorption spectroscopy of the OxyBP:BAC complex), we will examine the possibility of a type I interaction by probing the reactivity of OxyBP in its first excited singlet state. The amplitude of the signal is rather small because the constraint imposed on the sample was both to achieve nearly full binding and to avoid excessive scattering of the pump beam by too This journal is © The Royal Society of Chemistry and Owner Societies 2008 large BAC concentrations.…”

Section: Steady-state Irradiationmentioning

confidence: 99%

Steady-state and femtosecond photoinduced processes of blepharismins bound to alpha-crystallin

Youssef¹,

Brazard²,

Ley³

et al. 2008

Photochem Photobiol Sci

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The interaction of blepharismin (BP) and oxyblepharismin (OxyBP) with bovine alpha-crystallin (BAC) has been studied both by steady-state and femtosecond spectroscopy, with the aim of assessing the possible phototoxicity of these compounds toward the eye tissues. We showed that these pigments form with BAC potentially harmful ground-state complexes, the dissociation constants of which have been estimated to be 6 +/- 2 micromol L(-1) for OxyBP and 9 +/- 4 micromol L(-1) for BP. Irradiation with steady-state visible light of solutions of blepharismins in the presence of BAC proved to induce a quenching of both the pigment and the intrinsic protein fluorescences. These effects were tentatively rationalized in terms of structural changes of alpha-crystallin. On the other hand, femtosecond transient absorption spectroscopy was used to check the occurrence of any type I photoactivity of oxyblepharismin bound to alpha-crystallin. The existence of a particular type of fast photoinduced reaction, not observed in former studies with human serum albumin but present in the natural oxyblepharismin-binding protein, could here be evidenced but no specific reaction was observed during the first few nanoseconds after excitation. Partial denaturation of alpha-crystallin was however found to alter the excited-state behaviour of its complex with oxyblepharismin, making it partly resemble that of free oxyblepharismin in solution.

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“…Systemic administration of St. John's Wort at regular doses (1000 mg) produces serum levels of Hyp that are equivalent to a concentration of the order of 0.1 μ M (8). Nonnegligible concentrations of Hyp are reached even at the eye level, leading to potential damage of both the lens (9, 10) and retina. Hypericin at concentrations in the micromolar range have also been shown to cause inhibition in RPE cell proliferation and to induce apoptotic cell death (11).…”

Section: Introductionmentioning

confidence: 99%

Time‐resolved Microspectrofluorimetry and Fluorescence Lifetime Imaging of Hypericin in Human Retinal Pigment Epithelial Cells^¶

Taroni

Valentini

Comelli

et al. 2005

Photochem & Photobiology

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Hypericin is the active ingredient of the off‐the‐shelf antidepressant St. John's Wort. It is an effective phototoxic agent and its systemic administration at therapeutic doses could induce particular damage in the eye due to continuous light exposure. Hypercin is strongly fluorescent and its fluorescence properties can be monitored to investigate noninvasively its localization and interactions. To this aim, time‐resolved microspectrofluorimetry and fluorescence life‐time imaging were used to assess the spectral and temporal properties as well as the spatial distribution of the fluorescence emitted by retinal pigment epithelium (RPE) cells treated with Hyp at concentrations in the micromolar range (0.5–10 μM). In the presence of hypericin, the emission peaks at 600‐605 nm and the fluorescence decay is best fitted with three lifetimes (5.5‐7 ns, 1.9‐2.5 ns and < 0.8 ns). Spectral and temporal differences were observed between high (≥5 μM) and low hypericin concentrations. In particular, upon increasing concentration, the emission spectrum of the slow component broadens and its lifetime shortens. The latter change is observed also when high concentrations are reached locally, due to more efficient localization within the cell.

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Lens α-Crystallin and Hypericin: A Photophysical Mechanism Explains Observed Lens Damage†¶

Cited by 6 publications

References 40 publications

Christopher Foote's Discovery of the Role of Singlet Oxygen [¹O₂ (¹Δ_g)] in Photosensitized Oxidation Reactions

Christopher Foote's Discovery of the Role of Singlet Oxygen [¹O₂ (¹Δ_g)] in Photosensitized Oxidation Reactions

Steady-state and femtosecond photoinduced processes of blepharismins bound to alpha-crystallin

Time‐resolved Microspectrofluorimetry and Fluorescence Lifetime Imaging of Hypericin in Human Retinal Pigment Epithelial Cells^¶

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Lens α-Crystallin and Hypericin: A Photophysical Mechanism Explains Observed Lens Damage†¶

Cited by 6 publications

References 40 publications

Christopher Foote's Discovery of the Role of Singlet Oxygen [1O2 (1Δg)] in Photosensitized Oxidation Reactions

Christopher Foote's Discovery of the Role of Singlet Oxygen [1O2 (1Δg)] in Photosensitized Oxidation Reactions

Steady-state and femtosecond photoinduced processes of blepharismins bound to alpha-crystallin

Time‐resolved Microspectrofluorimetry and Fluorescence Lifetime Imaging of Hypericin in Human Retinal Pigment Epithelial Cells¶

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Christopher Foote's Discovery of the Role of Singlet Oxygen [¹O₂ (¹Δ_g)] in Photosensitized Oxidation Reactions

Christopher Foote's Discovery of the Role of Singlet Oxygen [¹O₂ (¹Δ_g)] in Photosensitized Oxidation Reactions

Time‐resolved Microspectrofluorimetry and Fluorescence Lifetime Imaging of Hypericin in Human Retinal Pigment Epithelial Cells^¶