TY - JOUR PY - 2007// TI - Calcium-activated butyrylcholinesterase in human skin protects acetylcholinesterase against suicide inhibition by neurotoxic organophosphates JO - Biochemical and biophysical research communications A1 - Schallreuter, Karin U. A1 - Gibbons, Nicholas C. J. A1 - Elwary, Souna M. A1 - Parkin, Susan M. A1 - Wood, John M. SP - 1069 EP - 1074 VL - 355 IS - 4 N2 - 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.
Language: en
LA - en SN - 0006-291X UR - http://dx.doi.org/10.1016/j.bbrc.2007.02.078 ID - ref1 ER -