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Increased oxidative-modifications of cytosolic proteins in 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-exposed rat liver

  1. Author:
    Upreti, V. V.
    Moon, K. H.
    Yu, L. R.
    Lee, I. J.
    Eddington, N. D.
    Ye, X.
    Veenstra, T. D.
    Song, B. J.

  2. Author Address

    [Upreti, Vijay V.; Eddington, Natalie D.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet & Biopharmaceut Lab, Baltimore, MD 21201 USA. [Moon, Kwan-Hoon; Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD USA. [Yu, Li-Rong; Ye, Xiaoying; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Lee, Insong J.] Coll Notre Dame Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD USA.;Song, BJ, NIAAA, Lab Membrane Biochem & Biophys, 5625 Fishers Lane,Room 2S-30, Rockville, MD 20852 USA.;bj.song@nih.gov
    1. Year: 2011
    2. Date: Jan
  2. Journal: Proteomics
    1. 11
    2. 2
    3. Pages: 202-211
  4. Type of Article: Article
  5. ISSN: 1615-9853
  1. Abstract:

    It is well established that 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) causes acute liver damage in animals and humans. The aim of this study was to identify and characterize oxidative modification and inactivation of cytosolic proteins in MDMA-exposed rats. Markedly increased levels of oxidized and nitrated cytosolic proteins were detected 12 h after the second administration of two consecutive MDMA doses (10 mg/kg each). Comparative 2-DE analysis showed markedly increased levels of biotin-N-methylimide-labeled oxidized cytosolic proteins in MDMA-exposed rats compared to vehicle-treated rats. Proteins in the 22 gel spots of strong intensities were identified using MS/MS. The oxidatively modified proteins identified include anti-oxidant defensive enzymes, a calcium-binding protein, and proteins involved in metabolism of lipids, nitrogen, and carbohydrates (glycolysis). Cytosolic superoxide dismutase was oxidized and its activity significantly inhibited following MDMA exposure. Consistent with the oxidative inactivation of peroxiredoxin, MDMA activated c-Jun N-terminal protein kinase and p38 kinase. Since these protein kinases phosphorylate anti-apoptotic Bcl-2 protein, their activation may promote apoptosis in MDMA-exposed tissues. Our results show for the first time that MDMA induces oxidative-modification of many cytosolic proteins accompanied with increased oxidative stress and apoptosis, contributing to hepatic damage.

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External Sources

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  2. DOI: 10.1002/pmic.201000203
  3. View record in Web of Science®
  4. WOS: 000285884400003

Library Notes

  1. Fiscal Year: FY2010-2011
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