The surface oxidation potential of human neuromelanin reveals a spherical architecture with a pheomelanin core and a eumelanin surface

Abstract

Neuromelanin (NM) isolated from the substantia nigra region of the human brain was studied by scanning probe and photoelectron emission microscopies. Atomic force microscopy reveals that NM granules are comprised of spherical structures with a diameter of Ϸ30 nm, similar to that observed for Sepia cuttlefish, bovine eye, and human eye and hair melanosomes. Photoelectron microscopy images were collected at specific wavelengths of UV light between 248 and 413 nm, using the spontaneous-emission output from the Duke OK-4 free electron laser. Analysis of the data establishes a threshold photoionization potential for NM of 4.5 ؎ 0.2 eV, which corresponds to an oxidation potential of ؊0.1 ؎ 0.2 V vs. the normal hydrogen electrode (NHE). The oxidation potential of NM is within experimental error of the oxidation potential measured for human eumelanosomes (؊0.2 ؎ 0.2 V vs. NHE), despite the presence of a significant fraction of the red pigment, pheomelanin, which is characterized by a higher oxidation potential (؉0.5 ؎ 0.2 V vs. NHE). Published kinetic studies on the early chemical steps of melanogenesis show that in the case of pigments containing a mixture of pheomelanin and eumelanin, of which NM is an example, pheomelanin formation occurs first with eumelanin formation predominantly occurring only after cysteine levels are depleted. Such a kinetic model would predict a structural motif with pheomelanin at the core and eumelanin at the surface, which is consistent with the measured surface oxidation potential of the Ϸ30-nm constituents of NM granules.free electron laser ͉ oxidative stress ͉ photoelectron imaging ͉ substantia nigra ͉ Parkinson's disease

New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals

“…2F). Based on the melanic compositions given by the above chemical degradation and the data obtained by spatial imaging, these results establish that all pigments studied have a spherical structure consisting of a pheomelanin core encased by eumelanin (12). The threshold potential corresponds to an electrochemical potential of Ϫ0.2 V vs. normal hydrogen electrode, and so the surface of intact pigments is not thermodynamically positioned to trigger oxidative damage in neurons.…”

“…Neuromelanin in the substantial nigra and locus coeruleus is an electron-dense brown/black pigment composed of aggregates of Ϸ30-nm diameter spheres with a pheomelanin core and eumelanin surface and a pheomelanin/eumelanin ratio of 3:1 (12,13). Eumelanin is characterized by dihydroxyindole groups formed by DA oxidation and is responsible for the metal-chelating ability of neuromelanin (14).…”

The Ultraviolet Absorption Coefficient of Melanosomes Decreases with Increasing Pheomelanin Content

“…[28][29][30] Third, the outermost pigment surface of these melanosomes is pure eumelanin, despite the significant difference in their overall pigment composition, consistent with a "casing" model of mixed melanogenesis (the pheomelanin present in the melanosome is encased by eumelanin). 5,6,[31][32][33][34] Therefore, with increased pheomelanin content, the outer eumelanin coating will be thinner.…”

The Red and the Black

“…This model is not unique to the iris melanosomes; neuromelanin granules isolated from various regions of the human brain also have such a structure. 43 The finding that pheomelanin is encapsulated by an excellent electron scavenger (eumelanin) in natural systems would suggest that the structure of the mel- casian. 47 All these results argue in support of the conclusion that increased pheomelanin content leads to an increased risk factor for cancer.…”