Identification of Alkylbenzene Sulfonate Surfactants Leaching from an Acrylonitrile Butadiene Rubber as Novel Inhibitors of Calcineurin Activity

Abstract

Calcineurin (CN) is a Ca²⁺/calmodulin (CaM) dependent serine/threonine protein phosphatase and plays important role in several cellular functions in both higher and lower eukaryotes. Here we report inhibition of CN by linear alkylbenzene sulfonate. The clue to the finding was obtained while identifying the inhibitory material leaching from acrylonitrile butadiene rubber used for packing. Using standard dodecylbenzene sulfonate (C₁₂-LAS), we obtained strong inhibition of CN with a half maximal inhibitory concentration of 9.3 µM, whereas analogs such as p-octylbenzene sulfonate and SDS hardly or only slightly affected CN activity. Three alkaline phosphatases, derived from shrimp, bacteria, and calf-intestine, which exhibit similar enzymatic activities to CN, were not inhibited by C₁₂-LAS at concentrations of up to 100 µM. Furthermore, C₁₂-LAS did not inhibit Ca²⁺/CaM-dependent myosin light chain kinase activity when tested at concentrations of up to 36 µM. The results indicate that C₁₂-LAS is a potent selective inhibitor of CN activity.