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 days of differentiation, markers of neural effects and oxidative stress were measured following exposure of PC12 cells to 1-50 mu M 4-HNE for 1-8 h. 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 4 h. 4-HNE also induced depletion of GSTP1-1 and increased intracellular Ca++, with the latter seen as early as 1 h after exposure. Responses at 8 h 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. (C) 2010 Elsevier Ltd. All rights reserved.