Structure and Reactivity of Melanins: Influence of Free Radicals and Metal Ions

Sealy, Roger C.; Felix, Christopher C.; Hyde, James S.; Swartz, Harold M.

doi:10.1016/b978-0-12-566504-9.50014-3

Cited by 141 publications

(110 citation statements)

References 112 publications

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“…3, shaded, top), although any of the intermediates produced during melanogenesis may be incorporated into the final polymer (7). For decades melanin has been known to exhibit photoinduced, longlived semiquinone-like free radicals (7,9,47). The creation of long-lived free radicals from an excited state requires special circumstances such as hydrogen abstraction or proton-coupled electron transfer.…”

Section: Discussionmentioning

confidence: 99%

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Melanin photoprotection in the human retinal pigment epithelium and its correlation with light-induced cell apoptosis

Seagle

Rezai

Kobori

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

100

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Time-resolved electron paramagnetic resonance (TREPR) spectroscopy was used to study melanin free radicals in human retinal pigment epithelium (RPE) cells and tyrosine-derived synthetic melanin. TREPR signal traces from RPE cells reveal in vivo light-induced melanin free radical photochemistry in more detail than previously known. Electron spin polarization reflecting a non-Boltzmann population within the energy levels of the spin system is observed in RPE cells as the result of the triplet state photoproduction and subsequent disappearance of free radicals in the melanin polymer. In a set of RPE cells cultured from individual sources, differences in optical absorption, continuous wave EPR spectra, and TREPR signals were correlated with apoptosis assays performed by flow cytometry. Continuous wave EPR spectra of RPE cells and TREPR of acidified synthetic melanin suggest that increased melanin aggregation provides an increase in photoprotection in the RPE cells that are relatively less susceptible to blue light-induced apoptosis.continuous wave EPR ͉ electron spin polarization ͉ time-resolved EPR I n the eye, retinal pigment epithelium (RPE) is a monolayer of cuboidal cells between the photoreceptors and choriocapillaris of the eye and is specialized to uptake, phagocytize, and recycle the outer segment of photoreceptors and retinaldehyde, the chromophore of rhodopsin (1). RPE cell death plays a major role in the pathogenesis of age-related macular degeneration, the leading cause of blindness in the population Ͼ60 years of age in the developed world (2). Possible reasons given for the degeneration of RPE cells are their exposure to high oxidative stress and damaging irradiation (2-6).The pigment melanin, found in RPE cells, is a heterogeneous polymer consisting of various monomers believed to be oxidation products of dopa (dihydroxyphenylalinine) derived from tyrosine (7). Melanin contains intrinsic, indolesemiquinone-like doublet-state radicals (8, 9). Extrinsic indolesemiquinone-like radicals are reversibly photogenerated under visible or UV irradiation (9). RPE melanin serves a photoprotective role by absorbing radiation and scavenging free radicals and reactive oxygen species (ROS) (8-11). Evidence also exists for a phototoxic role for melanin in RPE cells, especially in aged cells, including measurable ROS photoproduction (8,(12)(13)(14)(15)(16)(17)(18). Electron paramagnetic resonance (EPR) spectroscopy enables a sensitive and nondestructive analysis and differentiation of natural melanin (9,19,20). The photophysical, redox, and aggregation properties of melanin as well as its ability to bind metals, proteins, and drugs have stimulated numerous studies in chemical, physical, and medical research (8, 9). The diversity and interrelations of its properties and the lack of chemical structures have hampered a clear understanding of the roles of melanin in RPE cells (8,9). Nanosecond time-resolved (TR) EPR studies have not been reported despite the relevance of TREPR to the study of melanin photochemistry (9). El...

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Section: Discussionmentioning

confidence: 99%

“…The pigment melanin, found in RPE cells, is a heterogeneous polymer consisting of various monomers believed to be oxidation products of dopa (dihydroxyphenylalinine) derived from tyrosine (7). Melanin contains intrinsic, indolesemiquinone-like doublet-state radicals (8,9).…”

mentioning

confidence: 99%

Melanin photoprotection in the human retinal pigment epithelium and its correlation with light-induced cell apoptosis

Seagle

Rezai

Kobori

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

100

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“…Additional extrinsic free radicals are reversibly photogenerated in melanin under visible or UV irradiation (18,19). The monomers of melanin are oxidation products of tyrosine, and many different monomers may be combined to produce a native melanin, although RPE melanin is primarily composed of indolequinone species (19). Little information exists regarding the structure of melanin primarily because the heterogeneity of melanin aggregates complicates most conventional methods of determining biomolecular structure (18,20).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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Photoprotection of human retinal pigment epithelium cells against blue light-induced apoptosis by melanin free radicals from Sepia officinalis

Seagle

Gasyna

Mieler

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Cultured retinal pigment epithelium (RPE) cells can phagocytize large foreign particles. Heterogeneous melanin aggregates fromSepia officinalis, a species of cuttlefish, were fed to cultured human RPE cells to produce cells laden with Sepia melanin. Blue lightinduced apoptosis (BLIA) assays were performed by flow cytometry on parallel cultures consisting of RPE cells isolated from independent eyes and evenly divided into two cultures, one fed Sepia melanin and one containing only native melanin. After culturing and growth of the cells under blue light illumination for 7 days, the apoptosis percentage of all cultures indicated that Sepia feeding significantly reduced BLIA. To account for Sepia photoprotection, continuous-wave EPR and time-resolved EPR experiments were performed with parallel RPE cultures by using UV (355 nm) and green (532 nm) laser irradiation. Continuous-wave EPR spectra prove that the concentrations of intrinsic and extrinsic melanin free radicals in the Sepia-RPE culture are large compared with those concentrations in the RPE culture. Time-resolved EPR spectra indicate that both UV and green light produced extrinsic melanin radicals as radical pairs from the triplet manifold with a linear dependence on the number of photons per second. These experiments conclusively demonstrate that decreased RPE susceptibility to BLIA correlates with increased intracellular melanin free radical concentrations and that nonnative melanin can supplement native melanin photoprotection of RPE cells.age-related macular degeneration ͉ continuous-wave EPR ͉ time-resolved EPR

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Ultrastructural recognition of gap junctions between melanocytes in human vestibular organs by tannic acid containing fixative preparation and freeze-fracture technique

et al. 1996

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Structure and Reactivity of Melanins: Influence of Free Radicals and Metal Ions

Cited by 141 publications

References 112 publications

Melanin photoprotection in the human retinal pigment epithelium and its correlation with light-induced cell apoptosis

Melanin photoprotection in the human retinal pigment epithelium and its correlation with light-induced cell apoptosis

Photoprotection of human retinal pigment epithelium cells against blue light-induced apoptosis by melanin free radicals from Sepia officinalis

Ultrastructural recognition of gap junctions between melanocytes in human vestibular organs by tannic acid containing fixative preparation and freeze-fracture technique

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