Lysophosphatidylcholine induces apoptosis in AR42J cells.
Phospholipase A2 (PLA2) has been suggested to play an important role in the pathogenesis of acute pancreatitis, in part through the PLA2-generated phospholipid by-products, most notably lysophosphatidylcholine (lyso-PC). The effects of lyso-PC on pancreatic acinar cells, other than the induction of necrosis, are poorly characterized. Here we examined the effects of lyso-PC on the induction of apoptosis in rat pancreatic AR42J cells. Lyso-PC induced apoptosis in a dose-dependent manner at 10 and 25 microM, but induced cell lysis at > or = 50 microM. Lyso-PC-induced (at 25 microM) apoptosis was not blocked by a protein kinase C inhibitor (staurosporine) or by inhibitors of caspases (acetyl-DEVD-aldehyde and benzoyloxycarbonyl-VAD-fluoromethylketone). Lyso-PC at 10 and 25 microM induced the expression of clusterin mRNA and wild-type p53. Apoptosis induction by lyso-PC (at 25 microM) was not inhibited by a specific antagonist of platelet-activating factor (PAF) receptor, suggesting that the action was independent of th
Masamune
A
A
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan. amasamune@int3.med.tohoku.ac.jp
Sakai
Y
Y
Satoh
A
A
Fujita
M
M
Yoshida
M
M
Shimosegawa
T
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D061945:Caspase Inhibitors; D002460:Cell Line; D051152:Clusterin; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000235:genetics; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D061945:Caspase Inhibitors; D051152:Clusterin; D017931:DNA Primers; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D008244:Lysophosphatidylcholines; D018832:Molecular Chaperones; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D004247:DNA; D011493:Protein Kinase C