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http://dx.doi.org/10.4062/biomolther.2009.17.4.379

Arachidonic Acid Mediates Apoptosis Induced by N-Ethylmaleimide in HepG2 Human Hepatoblastoma Cells

Lee, Yong-Soo (College of Pharmacy, Duksung Women's University)

Publication Information

Biomolecules & Therapeutics / v.17, no.4, 2009 , pp. 379-387 More about this Journal

Abstract

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 $A_2$ ( $PLA_2$ )-arachidonic acid (AA) signals in the mechanism of the NEM-induced apoptosis. In these experiments we used arachidonyl trifluoromethylketone ( $AACOCF_3$ ), bromoenol lactone (BEL) and p-bromophenacyl bromide (BPB) as inhibitors of the calcium-dependent cytosolic $PLA_2$ ( $cPLA_2$ ), the calcium-independent $PLA_2$ ( $iPLA_2$ ) and the secretory $PLA_2$ ( $sPLA_2$ ), respectively. BEL significantly inhibited the NEM-induced apoptosis, whereas $AACOCF_3$ 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 $iPLA_2$ may mediate the NEMinduced apoptosis in HepG2 cells.

Keywords

N-Ethylmaleimide; Arachidonic acid; Apoptosis; $K^+$ ; $Cl^-$ -cotransport; Phospholipase $A_2$ ; HepG2 cell;

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