It has been demonstrated recently that rabbit renal proximal tubule cells (RPTC) express a novel Ca2+-independent phospholipase A2 (iPLA2) whose activity localizes to the endoplasmic reticulum (ER-iPLA2) and is similar to group VIB PLA2, In this study, the expression of group VIB PLA2 was examined and the role of ER-iPLA2 in cisplatin-induced apoptosis was determined. Cisplatin induced both time- and concentration-dependent RPTC apoptosis as determined by p53 nuclear localization, annexin V staining, caspase 3 activity, and chromatin condensation. Inhibition of ER-iPLA2 with bromoenol lactone (5 μM) reduced cisplatin-induced annexin V binding 40%, chromatin condensation 55%, and caspase 3 activity 42%, but had no effect on p53 nuclear localization. Treatment of RPTC with the protein kinase C stimulator phorbol 12-myristate 13-acetate increased the activity of ER-iPLA2 2-fold and increased cisplatin-induced RPTC apoptosis. These studies demonstrate that group VIB PLA2 is expressed in RPTC and suggest that RPTC ER-iPLA2 is the rabbit homolog of group VIB PLA2. These data also demonstrate that ER-iPLA2 acts downstream of p53 and upstream of caspase 3 to mediate cisplatin-induced RPTC apoptosis. Finally, ER-iPLA2 seems to be regulated by protein kinase C.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Mar 2004|
ASJC Scopus subject areas
- Molecular Medicine