The polymerization of melanin: a poorly understood phenomenon with egregious biological implications.

Abstract:

:Several hypotheses have explicitly implicated the role of an altered redox status of melanin in the aetiology of melanoma and macular degeneration. The balance between the intrinsic anti-oxidant and pro-oxidant properties of melanin is lost, resulting in an altered redox phenotype. We propose that such an alteration of the redox status of melanin may arise, in part, due to suboptimal conditions for the effective polymerization of melanin precursors. We suggest that a decrease in the degree of polymerization or molecular weight of the melanin polymer may cause an alteration of the redox status of the polymer towards a more pro-oxidant state. A higher propensity of smaller oligomers to complex metals, coupled with an upregulation of metallothionein expression, results in increased production of free radicals including the superoxide anion. This, in association with an increase in the rate of tyrosinase degradation, a decrease in the rate of tyrosinase activation, alterations to template protein structure or alterations in the kinetics of the oxidation of tyrosine via the Raper-Mason pathway, may result in an overcoming of the cellular anti-oxidant pool, an increased susceptibility to oxidative stress and alterations to the reaction kinetics of melanogenesis, thus setting up a cycle of increasing oxidative stress and proliferation leading to the leakage of melanin monomers outside the organelle, thereby causing cytotoxicity and necrosis.

journal_name

Melanoma Res

journal_title

Melanoma research

authors

Sarangarajan R,Apte SP

doi

10.1097/01.cmr.0000195699.35143.df

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

3-10

issue

1

eissn

0960-8931

issn

1473-5636

pii

00008390-200602000-00002

journal_volume

16

pub_type

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