Phospholipase A(2)-mediated Ca2+ influx by 2,2 ',4,6-tetrachlorobiphenyl in PC12 cells

Abstract

Polychlorinated biphenyls (PCBs) are a group of persistent and widespread environmental pollutants, and known to affect signaling molecules. Phospholipase A(2)(PLA(2)) mediates cellular destructive processes as well as normal physiological responses in neuronal cells. In this study, we examined whether PLA(2) can activated by PCBs in PC12 cells. Of the congeners tested, ortho-substituted PCBs were found to induce PLA(2) activation. PLA(2) activation by 2,2',4,6-tetrachlorobiphenyl (TeCB), the most potent congener, was inhibited by bromoenol lactone (BEL), a calcium-independent PLA(2) (iPLA(2)) inhibitor, and methyl arachidonyl fluorophosphonate (MAFP), a cytosolic PLA(2) and iPLA(2) inhibitor. In the case of Ca2+, although 2,2',4,6-TeCB increased [Ca2+](i) in the presence of extracellular Ca2+, PLA(2) activation was not inhibited by EGTA and 1,2-bis (o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra (acetoxy-mothyl) ester, an extracellular an an intracellular Ca2+ chelator, respectively. On the other hand, 2,2',4,6-TeCB-induced Ca2+ increase was partially inhibited by BEL and MAFP. In addition, 2,2',4,6-TeCB induced apoptotic cell death in these cells. Taken together, our results suggest that ortho-substituted PCBs might induce apoptosis through PLA(2)-mediated Ca2+ influx, which provides a clue to understand the mechanism of neurotoxic effects of ortho-substituted PCBs. (C) 2002 Elsevier Science.