NGF induced differentiated PC12 cells as in vitro tool to study 4-hydroxynonenal induced cellular damage

Investigations were carried out to examine the suitability of PC12 cells as an in vitro tool to examine 4-hydroxynonenal (4-HNE)-induced toxicity in nervous tissue. On day 8 of differentiation, markers of neural effects and oxidative stress were measured following exposure of PC12 cells to 1-50 microM 4-HNE for 1-8h. Endpoints included dopamine DA-D(2) receptor and glutathione S-transferase (GSTP1-1) protein levels, 4-HNE-protein binding, glutathione (GSH) concentrations and intracellular calcium levels. GSH levels were maximally depleted after 4h. 4-HNE also induced depletion of GSTP1-1 and increased intracellular Ca(++), with the latter seen as early as 1h after exposure. Responses at 8h were not greater than responses at earlier times. The experiments suggest that PC12 cells could be an in vitro tool for understanding toxicant-cell interactions, especially those that result in oxidative stress.