3,4-Methylenedioxymethamphetamine (MDMA) is an illicit psychoactive drug that has gained immense popularity among teenagers and young adults. The cardiovascular toxicological consequences of abusing this compound have not been fully characterized. The present study utilized a transient transfection/dual luciferase genetic reporter assay, fluorescence confocal microscopy, and gene expression macroarray technology to determine nuclear factor-κB (NF-κB) activity, intracellular calcium balance, mitochondrial depolarization, and gene transcription profiles, respectively, in cultured rat striated cardiac myocytes (H9c2) exposed to MDMA. At concentrations of 1×10−3 M and 1×10−2 M, MDMA significantly enhanced NF-κB reporter activity compared with 0 M (medium only) control. This response was mitigated by cotransfection with IκB for 1×10−3 M but not 1×10−2 M MDMA. MDMA significantly increased intracellular calcium at concentrations of 1×10−3 M and 1×10−2 M and caused mitochondrial depolarization at 1×10−2 M. MDMA increased the transcription of genes that are considered to be biomarkers in cardiovascular disease and genes that respond to toxic indults. Selected gene activation was verified via temperature-gradient RT-PCR conducted with annealing temperatures ranging from 50°C to 65°C. Collectively, these results suggest that MDMA may be toxic to the heart through its ability to activate the myocardial NF-κB response, disrupt cytosolic calcium and mitochondrial homeostasis, and alter gene transcription.
Original Publication Citation
Tiangco, D. A., Lattanzio Jr, F. A., Osgood, C. J., Beebe, S. J., Kerry, J. A., & Hargrave, B. Y. (2005). 3,4-Methylenedioxymethamphetamine activates nuclear factor-κB;, increases intracellular calcium, and modulates gene transcription in rat heart cells. Cardiovascular Toxicology, 5(3), 301-310. doi:10.1385/CT:5:3:301
Tiangco, David A.; Lattanzio, Frank A. Jr.; Osgood, Christopher J.; Beebe, Stephen J.; Kerry, Julie A.; and Hargrave, Barbara Y., "3,4-Methylenedioxymethamphetamine Activates Nuclear Factor- κB, Increases Intracellular Calcium, and Modulates Gene Transcription in Rat Heart Cells" (2005). Biological Sciences Faculty Publications. 381.