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  • 1
    Electronic Resource
    Electronic Resource
    Human epidermal acetylcholinesterase (AchE) is regulated by hydrogen peroxide (H2O2) (2005)
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    Details
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previously it has been demonstrated that the human epidermis synthesizes and degrades acetylcholine and expresses both muscarinic and nicotinic receptors. These cholinergic systems have been implicated in the development of the epidermal calcium gradient and differentiation in normal healthy skin. In vitiligo severe oxidative stress occurs in the epidermis of these patients with accumulation of H2O2 in the 10−3M range together with a decrease in catalase expression/activity due to deactivation of the enzyme active site. It was also shown that the entire recycling of the essential cofactor (6R)-L-erytho 5, 6, 7, 8 tetrahydrobiopterin via pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR) is affected by H2O2 oxidation of Trp/Met residues in the enzyme structure leading to deactivation of these proteins. Using fluorescence immunohistochemistry we now show that epidermal H2O2 in vitiligo patients yields also almost absent epidermal acetylcholinesterase (AchE) in association with accumulation of epidermal acetylcholine. This result was confirmed by Fluorescence excitation spectroscopy following the Trp fluorescence at λmax 280 nm. A kinetic analysis using pure recombinant human AchE revealed that low concentrations of H2O2(10−6M) activate this enzyme by increasing the Vmax 〉 2 fold, meanwhile high concentrations of H2O2(10−3M) deactivate the enzyme with a significant decrease in Vmax. Molecular modelling based on the established 3D structure of human AchE supported that H2O2-mediated oxidation of Trp432, Trp435 and Met436 moves and disorients the active site His440 of the enzyme, thus explaining the deactivation of the protein. To our knowledge these results identified for the first time H2O2 regulation of AchE. Moreover, it was shown that H2O2-mediated oxidation of AchE contributes significantly to the well established oxidative stress in vitiligo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0906-6705.2005.0266j.x
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  • 2
    Electronic Resource
    Electronic Resource
    Evidence for epidermal acetylcholine accumulation after oxidative stress by H2O2 and possible implications (2004)
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Experimental dermatology 13 (2004), S. 0 
    Details
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Acetylcholine (Ach) has been shown to be synthesized de novo and degraded in the human skin (1), while the presence of acetylcholinesterase (AchE), the degrading enzyme, was first mentioned in 1989 (2). It is now accepted that H2O2-related oxidative stress is a major player in the development/acceleration of vitiligo (3). This oxidative stress affects the recycling of the essential cofactor (6R)-l-erythro 5,6,7,8 tetrahydrobiopterin (6BH4) via H2O2-mediated oxidation of Trp and Met residues in the structure of pterin-4a carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR) (3). Only very recently, it was recognized that AchE is also affected and deactivated by 10−3 m H2O2 causing the accumulation of Ach in the epidermis of patients with vitiligo (4). One of the implications of oxidative stress in vitiligo includes pruritus, which was for a long time attributed to the presence of epidermal H2O2 in the 10−3 m range. In this context, a role for Ach has been suggested in association with pruritus, and therefore, we would like to suggest that Ach accumulation caused by H2O2-mediated deactivation of AchE may well initiate pruritus (5). The Ach accumulation can also explain the earlier documented decreased sweating in patients with vitiligo (6).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0906-6705.2004.0212ce.x
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    Paper (German National Licenses)
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