Zinc inhibits p75NTR-mediated apoptosis in chick neural retina.

It has previously been documented that Zn2+ inhibits TrkA-mediated effects of NGF. To evaluate the ability of Zn2+ to attenuate the biological activities of NGF mediated by p75NTR, we characterized the effects of this transition metal cation on both binding and the pro-apoptotic properties of the NGF-p75NTR interaction. Binding of NGF to p75NTR displayed higher affinity in embryonic chick retinal cells than in PC12 cells. NGF induced apoptosis in dissociated cultures of chick neural retina. The addition of 100 microM Zn2+ inhibited binding and chemical cross-linking of 125I-NGF to p75NTR, and also attenuated apoptosis mediated by this ligand-receptor interaction. These studies lead to the conclusion that Zn2+ antagonizes NGF/p75NTR-mediated signaling, suggesting that the effect of this transition metal cation can be either pro- or anti-apoptotic depending on the cellular context.