Protective Effect of Geranylgeranylacetone against Methamphetamine-Induced Neurotoxicity in Rat Pheochromocytoma Cells

Background: Methamphetamine is a central nervous system stimulant and is one of the agents most commonly abused by illicit drug users which could induce neuron apoptosis when it is used repeatedly and overdosed. Our previous study demonstrated that geranylgeranylacetone (GGA) was an inducer of thioredoxin-1 (Trx-1) and heat shock protein 70 (Hsp70), which played a cytoprotective role against neurotoxicity. Methods: Using the MTT assay, we detected the effect of GGA on cell viability by methamphetamine in rat pheochromocytoma (PC12) cells. Tyrosine hydroxylase, Trx-1, Hsp70, procaspase-9, procaspase-12 and procaspase-3 expression were examined by Western blot analysis. We also detected enzymatic activities of caspase-3 and caspase-9. Results: We found that GGA protected PC12 cells from apoptosis caused by methamphetamine. Furthermore, GGA reversed the decreases in Trx-1 and Hsp70 by methamphetamine, and prevented the methamphetamine-induced decreases in procaspase-9 and procaspase-3. On the other hand, GGA prevented the methamphetamine-induced increases in the enzymatic activity of caspase-9 and caspase-3. Procaspase-1 2 was not changed by any treatment. Conclusions: These results indicate that GGA protects PC12 cells from methamphetamine-induced toxicity by increasing Trx-1 and Hsp70 and by preventing mitochondria pathway-mediated apoptosis. In summary, GGA may be used as a therapy for neurotoxicity induced by methamphetamine. (C) 2013 S. Karger AG, Basel