Neuroprotective effects of gangliosides on pardaxin-induced toxicity in PC12 cells

Pardaxin-induced cytotoxicity in PC12 cells represents a model system for the study of mechanisms underlying neuronal degeneration, as well as a tool for the evaluation of potential neuroprotective agents. In the present investigation, viability of PC12 cells following exposure to pardaxin (1-20 μM), was assessed in parallel to the determination of PGE₂ content in the culture medium. A series of gangliosides (GM1, GM2, GM3, GD1a, and GQ1b) were found to have a protective effect on pardaxin-induced cytotoxicity and to inhibit the production of PGE₂. In contrast, the neurotrophins NGF and FGF, and the Ca-channel blocker nifedipine, had no effect on survival or on PGE₂ production. Inhibitors of PGE₂ release did not improve survival, suggesting that the apparent association between PX-induced PGE₂ release and cytotoxicity are independent events.