Abstract
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 μM, but induced cell lysis at ≥50 μM. Lyso-PC-induced (at 25 μM) 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 μM induced the expression of clusterin mRNA and wild-type p53. Apoptosis induction by lyso-PC (at 25 μM) was not inhibited by a specific antagonist of platelet-activating factor (PAF) receptor, suggesting that the action was independent of the PAF receptor. These molecular events suggest a novel role of lyso-PC in the modulation of acinar cell function.
| Original language | English |
|---|---|
| Pages (from-to) | 75-83 |
| Number of pages | 9 |
| Journal | Pancreas |
| Volume | 22 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2001 |
Keywords
- Acute pancreatitis
- Apoptosis
- Lysophosphatidylcholine
- Phospholipase A2
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Hepatology
- Endocrinology
