title: Protective effect of geranylgeranylacetone against methamphetamine-induced neurotoxicity in rat pheochromocytoma cells.
abstract: 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-12 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.
authors.affiliation: Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lv
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.forename: Jinjing
authors.initials: J
authors.lastname: Jia
authors.forename: Zhizhou
authors.initials: Z
authors.lastname: Shi
authors.forename: Jie
authors.initials: J
authors.lastname: Bai
mesh_terms: D000310:Adrenal Gland Neoplasms; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D008694:Methamphetamine / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D016716:PC12 Cells; D010673:Pheochromocytoma; D051381:Rats; D013879:Thioredoxins / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents; C495697:Txn1 protein, rat; D008694:Methamphetamine; D013879:Thioredoxins; D014446:Tyrosine 3-Monooxygenase; D020169:Caspases; C031049:geranylgeranylacetone