Activity of protein kinase C modulates the apoptosis induced by polychlorinated biphenyls in human leukemic HL-60 cells.
Polychlorinated biphenyls (PCBs) induce apoptotic cell death of HL-60 cells. In the present study, we examined the possible involvement of protein kinase C (PKC) in PCB-induced apoptosis of HL-60 cells. Treatment of cells with phorbol 12-myristate 13-acetate (PMA), an activator of PKC, suppressed DNA fragmentation induced by PCBs in HL-60 cells. Treatment with another active phorbol ester, phorbol-12,13-dibutyrate (PDBu), also suppressed PCB-induced DNA fragmentation, whereas 4alpha-phorbol-12,13-didecanoate (4alphaPDD), an inactive phorbol ester, did not affect PCB-induced apoptosis of HL-60 cell. Moreover, 1-oleoyl-2-acetyl-sn-glycerol (OAG), an activator of PKC that is not a phorbol ester, also suppressed PCB-induced DNA fragmentation. However, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), an inhibitor of PKC, increased DNA fragmentation induced by PCBs. These results demonstrate that the activation of PKC is responsible for the suppression of PCB-induced apoptosis of HL-60 cells. Furthermore, inhibition of PKC promotes DNA fragmentation of HL-60 cells treated with PCBs, thereby suggesting the involvement of PKC activity in PCB-induced apoptosis of HL-60 cells.
Shin
Ho-Jung
HJ
Department of Biology, Kyonggi University, Suwon, 440-760, Kyonggi-Do, South Korea.
Gye
Myung-han
MH
Chung
Kyu-Hoi
KH
Yoo
Byung-Sun
BS
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020111:Chlorodiphenyl (54% Chlorine) / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects*; D004075:Diglycerides / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D004791:Enzyme Inhibitors; D010703:Phorbol Esters; D020111:Chlorodiphenyl (54% Chlorine); C008876:phorbol-12,13-didecanoate; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate