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Oxidative stress-mediated inhibition of brain creatine kinase activity by methylmercury.
- Source :
-
Neurotoxicology [Neurotoxicology] 2010 Sep; Vol. 31 (5), pp. 454-60. Date of Electronic Publication: 2010 Jun 04. - Publication Year :
- 2010
-
Abstract
- Methylmercury (MeHg), a potent neurotoxicant, easily passes through the blood-brain barrier and accumulates in brain causing severe irreversible damage. However, the underlying neurotoxic mechanisms elicited by MeHg are still not completed defined. In this study, we aimed to investigate the in vitro toxic effects elicited by crescent concentrations (0-1500 microM) of MeHg on creatine kinase (CK) activity, thiol content (NPSH) and protein carbonyl content (PCC) in mouse brain preparations. In addition, CK activity, MTT reduction and DCFH-DA oxidation (reactive oxygen species (ROS) formation) were also measured in C6 glioma cell linage. CK activity was severely reduced by MeHg treatment in mouse brain preparations. This inhibitory effect was positively correlated to the MeHg-induced reduction of NPSH levels and increment in PCC. Moreover, the positive correlation between brain CK activity and NPSH levels was observed at either 15 or 60 min of MeHg pre-incubation. In addition, MeHg-treated C6 cells showed also a significant inhibition of CK activity at MeHg concentrations, as low as, 50 microM in parallel to reduced mitochondrial function and increased ROS production. Taking together, these data demonstrate that MeHg severely affects CK activity, an essential enzyme for brain energy buffering to maintain cellular energy homeostasis. This effect appears to be mediated by oxidation of thiol groups that might cause subsequent oxidative stress.<br /> (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Subjects :
- Analysis of Variance
Animals
Astrocytoma pathology
Brain enzymology
Cell Line, Tumor
Dose-Response Relationship, Drug
Enzyme Activation drug effects
Male
Mice
Protein Carbonylation drug effects
Reactive Oxygen Species metabolism
Tetrazolium Salts
Thiazoles
Time Factors
Brain drug effects
Creatine Kinase metabolism
Gene Expression Regulation, Enzymologic drug effects
Methylmercury Compounds pharmacology
Oxidative Stress drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9711
- Volume :
- 31
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Neurotoxicology
- Publication Type :
- Academic Journal
- Accession number :
- 20566354
- Full Text :
- https://doi.org/10.1016/j.neuro.2010.05.012