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Schallreuter KU, Gibbons NC, Elwary SM, Parkin SM, Wood JM: Calcium-activated butyrylcholinesterase in human skin protects acetylcholinesterase against suicide inhibition by neurotoxic organophosphates. Biochem Biophys Res Commun. 2007 Apr 20;355(4):1069-74. Epub 2007 Feb 23.
The human epidermis holds an autocrine acetylcholine production and degradation including functioning membrane integrated and cytosolic butyrylcholinesterase (BuchE). Here we show that BuchE activities increase 9-fold in the presence of calcium (0.5x10 (-3) M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. (45) Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H (2) O (2)-mediated oxidation. Moreover, we confirmed the faster hydrolysis by calcium-activated BuchE using the neurotoxic organophosphate O-ethyl-O-(4-nitrophenyl)-phenylphosphonothioate (EPN). Considering the large size of the human skin with 1.8m (2) surface area with its calcium gradient in the 10 (-3) M range, our results implicate calcium-activated BuchE as a major protective mechanism against suicide inhibition of AchE by organophosphates in this non-neuronal tissue. |
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