Peroxynitrite-mediated release of arachidonic acid from PC12 cells

A short term exposure of PC12 cells to a concentration of tert-butylhydrope roxide (tB-OOH) causing peroxynitrite-dependent DNA damage and cytotoxitici ty promoted a release of arachidonic acid (AA) that was sensitive to phosph olipase A(2) (PLA(2)) inhibitors and insensitive to phospholipase C or diac ylglycerol lipase inhibitors. The extent of AA release was also mitigated b y nitric oxide synthase (NOS) inhibitors and peroxpnitrite scavengers. Low levels (10 mu M) of authentic peroxynitrite restored the release of AA medi ated by tB-OOH in NOS-inhibited cells whereas concentrations of peroxynitri te of 20 mu M, or higher, effectively stimulated a PLA(2) inhibitor-sensiti ve release of AA also in the absence of additional treatments. These result s are consistent with the possibility that endogenous as well as exogenous peroxynitrite promotes activation of PLA(2).