PMID- 18780394
OWN - NLM
STAT- MEDLINE
DCOM- 20081202
LR  - 20220311
IS  - 1615-9861 (Electronic)
IS  - 1615-9853 (Print)
IS  - 1615-9853 (Linking)
VI  - 8
IP  - 18
DP  - 2008 Sep
TI  - Mechanism of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-mediated 
      mitochondrial dysfunction in rat liver.
PG  - 3906-18
LID - 10.1002/pmic.200800215 [doi]
AB  - Despite numerous reports citing the acute hepatotoxicity caused by 
      3,4-methylenedioxymethamphetamine (MDMA) (ecstasy), the underlying mechanism of 
      organ damage is poorly understood. We hypothesized that key mitochondrial 
      proteins are oxidatively modified and inactivated in MDMA-exposed tissues. The 
      aim of this study was to identify and investigate the mechanism of inactivation 
      of oxidatively modified mitochondrial proteins, prior to the extensive 
      mitochondrial dysfunction and liver damage following MDMA exposure. MDMA-treated 
      rats showed abnormal liver histology with significant elevation in plasma 
      transaminases, nitric oxide synthase, and the level of hydrogen peroxide. 
      Oxidatively modified mitochondrial proteins in control and MDMA-exposed rats were 
      labeled with biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized 
      proteins, purified with streptavidin-agarose, and resolved using 2-DE. 
      Comparative 2-DE analysis of biotin-NM-labeled proteins revealed markedly 
      increased levels of oxidatively modified proteins following MDMA exposure. Mass 
      spectrometric analysis identified oxidatively modified mitochondrial proteins 
      involved in energy supply, fat metabolism, antioxidant defense, and chaperone 
      activities. Among these, the activities of mitochondrial aldehyde dehydrogenase, 
      3-ketoacyl-CoA thiolases, and ATP synthase were significantly inhibited following 
      MDMA exposure. Our data show for the first time that MDMA causes the oxidative 
      inactivation of key mitochondrial enzymes which most likely contributes to 
      mitochondrial dysfunction and subsequent liver damage in MDMA-exposed animals.
FAU - Moon, Kwan-Hoon
AU  - Moon KH
AD  - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol 
      Abuse and Alcoholism, Bethesda, MD 20892-9410, USA.
FAU - Upreti, Vijay V
AU  - Upreti VV
FAU - Yu, Li-Rong
AU  - Yu LR
FAU - Lee, Insong J
AU  - Lee IJ
FAU - Ye, Xiaoying
AU  - Ye X
FAU - Eddington, Natalie D
AU  - Eddington ND
FAU - Veenstra, Timothy D
AU  - Veenstra TD
FAU - Song, Byoung-Joon
AU  - Song BJ
LA  - eng
GR  - N01CO12400/CA/NCI NIH HHS/United States
GR  - Z01 AA000036-21/ImNIH/Intramural NIH HHS/United States
GR  - Z99 AA999999/ImNIH/Intramural NIH HHS/United States
GR  - N01-CO-12400/CO/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PL  - Germany
TA  - Proteomics
JT  - Proteomics
JID - 101092707
RN  - 0 (Hallucinogens)
RN  - 0 (Maleimides)
RN  - 2519R1UGP8 (maleimide)
RN  - 6SO6U10H04 (Biotin)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 2.6.1.- (Transaminases)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Biotin/chemistry
MH  - Hallucinogens/*pharmacology
MH  - Hydrogen Peroxide/metabolism
MH  - Liver/metabolism/pathology
MH  - Male
MH  - Maleimides/chemistry
MH  - Mitochondria, Liver/*drug effects/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Nitric Oxide Synthase/blood
MH  - Oxidation-Reduction
MH  - Oxidative Stress
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tandem Mass Spectrometry/methods
MH  - Transaminases/blood
PMC - PMC2590641
MID - NIHMS69096
EDAT- 2008/09/10 09:00
MHDA- 2008/12/17 09:00
PMCR- 2009/09/01
CRDT- 2008/09/10 09:00
PHST- 2008/09/10 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/09/10 09:00 [entrez]
PHST- 2009/09/01 00:00 [pmc-release]
AID - 10.1002/pmic.200800215 [doi]
PST - ppublish
SO  - Proteomics. 2008 Sep;8(18):3906-18. doi: 10.1002/pmic.200800215.