Calcium-activated butyrylcholinesterase in human skin protects acetylcholinesterase against suicide inhibition by neurotoxic organophosphates.
Publication date
2007Keyword
Human epidermisHydrogen peroxide
Acetylcholinesterase
Calcium
EF-hand
Organophosphates
Butyrylcholinesterase
Peer-Reviewed
YesOpen Access status
closedAccess
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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 (0.5 × 10-3 M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. 45Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H2O2-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 1.8 m2 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 tissueVersion
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Schallreuter KU, Gibbons NC, Elwary SM, Parkin SM and Wood JM (2007) Calcium-activated butyrylcholinesterase in human skin protect acetylcholinesterase against suicide inhibition by neurotoxic organophosphates. Biochemical and Biophysical Research Communications. 355(4): 1069-1074.Link to Version of Record
https://doi.org/10.1016/j.bbrc.2007.02.078Type
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.1016/j.bbrc.2007.02.078