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KMID : 0606920090170040379
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Biomolecules & Therapeutics
2009 Volume.17 No. 4 p.379 ~ p.387
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Arachidonic Acid Mediates Apoptosis Induced by N-Ethylmaleimide in HepG2 Human Hepatoblastoma Cells
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Lee Yong-Soo
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Abstract
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We have previously reported that N-ethylmaleimide (NEM) induces apoptosis through activation of K＋, Cl?-cotransport (KCC) in HepG2 human hepatoblastoma cells. In this study we investigated the possible role of phospholipase A2 (PLA2)-arachidonic acid (AA) signals in the mechanism of the NEM-induced apoptosis. In these experiments we used arachidonyl trifluoromethylketone (AACOCF3), bromoenol lactone (BEL) and p-bromophenacyl bromide (BPB) as inhibitors of the calcium-dependent cytosolic PLA2 (cPLA2), the calcium-independent PLA2 (iPLA2) and the secretory PLA2 (sPLA2), respectively. BEL significantly inhibited the NEM-induced apoptosis, whereas AACOCF3 and BPB did not. NEM increased AA liberation in a dose-dependent manner, which was markedly prevented only by BEL. In addition AA by itself induced K＋ efflux, a hallmark of KCC activation, which was comparable to that of NEM. The NEM-induced apoptosis was not significantly altered by treatment with indomethacin (Indo) and nordihydroguaiaretic acid (NDGA), selective inhibitors of cyclooxygenase (COX) and lipoxygenase (LOX), respectively. Treatment with AA or 5,8,11,14-eicosatetraynoic acid (ETYA), a non-metabolizable analogue of AA, significantly induced apoptosis. Collectively, these results suggest that AA liberated through activation of iPLA2 may mediate the NEM- induced apoptosis in HepG2 cells.
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KEYWORD
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N-Ethylmaleimide, , Arachidonic acid, Apoptosis, K＋,Cl--cotransport, Phospholipase A2, HepG2 cell
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