Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Methamphetamine and MDMA (3,4-methylenedioxymethamphetamine) Induce Apoptosis in Both Human Serotonergic and Dopaminergic Cell Lines

  • Kim, Kyu Bong (Division of Safety Evaluation, National Institute of Toxicological Research, KFDA) ;
  • Suh, Soo Kyung (Division of Safety Evaluation, National Institute of Toxicological Research, KFDA) ;
  • Lee, Bo Kyung (Division of Safety Evaluation, National Institute of Toxicological Research, KFDA) ;
  • Kim, Byung Kyu (Division of Safety Evaluation, National Institute of Toxicological Research, KFDA) ;
  • Kim, Jae Hee (Division of Safety Evaluation, National Institute of Toxicological Research, KFDA) ;
  • Han, Eui Sik (Division of Safety Evaluation, National Institute of Toxicological Research, KFDA) ;
  • Park, Chang Won (Division of Safety Evaluation, National Institute of Toxicological Research, KFDA) ;
  • Kim, Jong Won (Division of Safety Evaluation, National Institute of Toxicological Research, KFDA) ;
  • Kim, Kwang Jin (Division of Safety Evaluation, National Institute of Toxicological Research, KFDA) ;
  • Lee, Sun Hee (Division of Safety Evaluation, National Institute of Toxicological Research, KFDA)
  • Published : 2003.12.01
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Abstract

Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) have become popular recreational drugs of abuse in many countries. Although the neurotoxic damage caused by METH and MDMA is characterized by degeneration of the dopaminergic and serotonergic systems in brain, the molecular and cellular mechanisms remain to be clarified. Therefore, the purposes of this study were to confirm the capability of METH and MDMA to induce apoptosis and to clarify the action of its molecular mechanism by using serotonergic JAR cells and dopaminergic SK-N-SH cells. METH and MDMA were dose-dependently cytotoxic to human serotonergic JAR cells and dopaminergic SK-N-SH cells. The morphological change of apoptosis was found in Giemsa staining and TUNEL and further verified in DNA fragmentation analysis. Immunoblotting analysis revealed proteolytic cleavage of caspase-3 and -9 and change of bcl-2 and bax proteins. These results suggest that METH and MDMA may induce caspase-dependent apoptosis via the mitochondrial cell death pathway and METH and MDMA-induced neurotoxicity may happen to broadly and independently of both dopaminergic and serotonergic systems.

Keywords

References

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