Original Paper

Anti-Apoptotic Effects of Arachidonic Acid and Prostaglandin E₂ in Pancreatic -Cells
Alexandros Papadimitriou, Aileen King, Peter Jones, Shanta Persaud

Beta Cell Development & Function Group, School of Biomedical & Health Sciences, King’s College London, London

Address of Corresponding Author

Cell Physiol Biochem 2007;20:607-616 (DOI: 10.1159/000107544)

  Key Words

• -cells
• Caspase-3
• Apoptosis
• Arachidonic acid
• Prostaglandin E₂

  Abstract

Background/Aims: The polyunsaturated fatty acid arachidonic acid (AA) has been implicated in -cell defence mechanisms and prostaglandin (PG) products of cyclooxygenase (COX) 2 action confer resistance to alloxan-induced apoptosis in insulin-secreting RIN cells. We have now investigated the anti-apoptotic effects of AA and its metabolite, PGE₂, in the MIN6 mouse insulin-secreting -cell line and mouse islets. Methods: Apoptosis was determined in MIN6 -cell and mouse islet extracts by measurement of capase-3 activity, and COX2 mRNA levels were quantified by real-time RT-PCR. Results: Exposure of MIN6 cells to AA (3.1-12.5µM) caused concentration-dependent reductions in apoptosis, and similar results were obtained when endogenous AA levels were elevated in cytosolic phospholipase A₂-overexpressing MIN6 cells. 25mM glucose caused both a significant up-regulation of MIN6 cell COX2 mRNA levels and a decrease in apoptosis. Inhibition of MIN6 cell COX2 activity with a selective inhibitor, NS-398 (10-100µM), increased apoptosis and exogenous PGE₂ (0.2-5µM) reduced NS-398-induced apoptosis in a concentration-dependent manner. The protective effects of AA and PGE₂ were also observed in primary mouse islets. Conclusion: These data show that AA and its COX2-generated metabolite, PGE₂, can protect -cells from apoptosis.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Dr. Shanta Persaud
Room 2.9N, Hodgkin Building King’s College London (GB)
Guy’s campus, London SE1 1UL
Tel. +44-20 7848 6275
E-Mail shanta.persaud@kcl.ac.uk

  Article Information

Accepted: May 31, 2007
Number of Print Pages : 10