Arachidonic Acid Activates K-Cl-cotransport in HepG2 Human Hepatoblastoma Cells.
Abstract
K(+)-Cl(-)-cotransport (KCC) has been reported to have various cellular functions, including proliferation and apoptosis of human cancer cells. However, the signal transduction pathways that control the activity of KCC are currently not well understood. In this study we investigated the possible role of phospholipase A(2) (PLA(2))-arachidonic acid (AA) signal in the regulatory mechanism of KCC activity. Exogenous application of AA significantly induced K(+) efflux in a dose-dependent manner, which was completely blocked by R-(+)-[2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl]oxy]acetic acid (DIOA), a specific KCC inhibitor. N-Ethylmaleimide (NEM), a KCC activator-induced K(+) efflux was significantly suppressed by bromoenol lactone (BEL), an inhibitor of the calcium-independent PLA(2) (iPLA(2)), whereas it was not significantly altered by arachidonyl trifluoromethylketone (AACOCF(3)) and p-bromophenacyl bromide (BPB), inhibitors of the calcium-dependent cytosolic PLA(2) (cPLA(2)) and the secretory PLA(2) (sPLA(2)), respectively. NEM increased AA liberation in a dose- and time-dependent manner, which was markedly prevented only by BEL. In addition, the NEM-induced ROS generation was significantly reduced b...Continue Reading
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