Increased oxidative-modifications of cytosolic proteins in 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-exposed rat liver.
Vijay Upreti, Kwan–hoon Moon, Li‐rong Yu, Insong J. Lee, Natalie D. Eddington, Xiaoying Ye, Timothy D. Veenstra, Byoung‐joon Song
PROTEOMICS January 2011 DOI: 10.1002/pmic.201000203 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal experiment Peer reviewed |
|---|---|
| Population | MDMA-exposed rats |
| Intervention | MDMA |
| Dose | 10 mg/kg each, two consecutive doses |
| Duration | 12 h after the second administration of two consecutive MDMA doses |
| Measures | 2-DE analysis, biotin-N-methylimide labeling, MS/MS |
| Topics | MDMA |
| Key findings | MDMA administration in rats increased oxidized and nitrated cytosolic liver proteins and inhibited cytosolic superoxide dismutase activity. The authors identified 22 gel spots of oxidatively modified proteins, including antioxidant enzymes and metabolic proteins, and report that MDMA activated JNK and p38 kinase, which they propose may promote apoptosis and contribute to hepatic damage. |
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 2
- A reconsideration and response to Parrott AC (2013) "Human psychobiology of MDMA or 'Ecstasy': an overview of 25 years of empirical research". Human Psychopharmacology: Clinical and Experimental March 1, 2014
- Acute administration of 3,4-methylenedioxymethamphetamine (MDMA) induces oxidative stress, lipoperoxidation and TNFα-mediated apoptosis in rat liver. Pharmacological Research August 12, 2011
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and 10 more in the library