Peroxynitrite‐mediated release of arachidonic acid from PC12 cells

A short term exposure of PC12 cells to a concentration of tert ‐butylhydroperoxide (tB‐OOH) causing peroxynitrite‐dependent DNA damage and cytotoxiticity promoted a release of arachidonic acid (AA) that was sensitive to phospholipase A 2 (PLA 2 ) inhibitors and insensitive to phospholipase C or diacylglycerol lipase inhibitors. The extent of AA release was also mitigated by nitric oxide synthase (NOS) inhibitors and peroxynitrite scavengers. Low levels (10 μ M ) of authentic peroxynitrite restored the release of AA mediated by tB‐OOH in NOS‐inhibited cells whereas concentrations of peroxynitrite of 20 μ M , or higher, effectively stimulated a PLA 2 inhibitor‐sensitive release of AA also in the absence of additional treatments. These results are consistent with the possibility that endogenous as well as exogenous peroxynitrite promotes activation of PLA 2 . British Journal of Pharmacology (2000) 129 , 1539–1542; doi: 10.1038/sj.bjp.0703275