ELEVATED CPLA(2) LEVELS AS A MECHANISM BY WHICH THE P70 TNF AND P75 NGF RECEPTORS ENHANCE APOPTOSIS

The 70-kDa TNF cell surface receptor (p70TNFR) and the related 75-kDa nerve growth factor (NGF) receptor (p75NGFR) can enhance cell death. E xpression of p70TNFR or p75NGFR in HeLa cells resulted in enhanced TNF -induced apoptotic cell death with a corresponding elevation of cytoso lic phospholipase A(2) (cPLA(2)) levels, This response was apparent by 24 h, did not occur with NGF treatment or when vector or TrkA NGFR we re expressed and was reversed by dexamethasone pretreatment. These fin dings reveal a novel mechanism by which the p70TNFR and p75NGFR achiev e enhanced TNFR-mediated programmed cell death by elevating cPLA(2) le vels.