PMID- 16244375
OWN - NLM
STAT- MEDLINE
DCOM- 20060105
LR  - 20191109
IS  - 1530-7905 (Print)
IS  - 1530-7905 (Linking)
VI  - 5
IP  - 3
DP  - 2005
TI  - 3,4-Methylenedioxymethamphetamine activates nuclear factor-kappaB, increases 
      intracellular calcium, and modulates gene transcription in rat heart cells.
PG  - 301-10
AB  - 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-kappaB (NF-kappaB) 
      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 x 10(-3) M and 1 x 10(-2) M, MDMA 
      significantly enhanced NF-kappaB reporter activity compared with 0 M (medium 
      only) control. This response was mitigated by cotransfection with IkappaB for 1 x 
      10(-3) M but not 1 x 10(-2) M MDMA. MDMA significantly increased intracellular 
      calcium at concentrations of 1 x 10(-3) M and 1 x 10(-2) M and caused 
      mitochondrial depolarization at 1 x 10(-2) M. MDMA increased the transcription of 
      genes that are considered to be biomarkers in cardiovascular disease and genes 
      that respond to toxic insults. Selected gene activation was verified via 
      temperature-gradient RT-PCR conducted with annealing temperatures ranging from 50 
      degrees C to 65 degrees C. Collectively, these results suggest that MDMA may be 
      toxic to the heart through its ability to activate the myocardial NF-kappaB 
      response, disrupt cytosolic calcium and mitochondrial homeostasis, and alter gene 
      transcription.
FAU - Tiangco, David A
AU  - Tiangco DA
AD  - Department of Biological Sciences, Old Dominion University, Norfolk, VA 23529, 
      USA.
FAU - Lattanzio, Frank A Jr
AU  - Lattanzio FA Jr
FAU - Osgood, Christopher J
AU  - Osgood CJ
FAU - Beebe, Stephen J
AU  - Beebe SJ
FAU - Kerry, Julie A
AU  - Kerry JA
FAU - Hargrave, Barbara Y
AU  - Hargrave BY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cardiovasc Toxicol
JT  - Cardiovascular toxicology
JID - 101135818
RN  - 0 (Hallucinogens)
RN  - 0 (NF-kappa B)
RN  - EC 1.13.12.- (Luciferases)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*metabolism
MH  - Cells, Cultured
MH  - Gene Expression/*drug effects
MH  - Genes, Reporter/drug effects/genetics
MH  - Hallucinogens/*pharmacology
MH  - Luciferases/metabolism
MH  - Microscopy, Confocal
MH  - Mitochondria, Heart/drug effects/metabolism
MH  - Myocytes, Cardiac/drug effects/*metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - NF-kappa B/*biosynthesis/genetics
MH  - Oligonucleotide Array Sequence Analysis
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2005/10/26 09:00
MHDA- 2006/01/06 09:00
CRDT- 2005/10/26 09:00
PHST- 2005/10/26 09:00 [pubmed]
PHST- 2006/01/06 09:00 [medline]
PHST- 2005/10/26 09:00 [entrez]
AID - CT:5:3:301 [pii]
AID - 10.1385/ct:5:3:301 [doi]
PST - ppublish
SO  - Cardiovasc Toxicol. 2005;5(3):301-10. doi: 10.1385/ct:5:3:301.