The mitochondrial toxin, 3-nitropropionic acid, induces extracellular Zn2+ accumulation in rat hippocampus slices.

Abstract

3-nitropropionic acid (3-NPA), a suicide inhibitor of succinate dehydrogenase (SDH; complex II), has been used to provide useful experimental models of Huntington's disease (HD) and "chemical hypoxia" in rodents. The trace ion Zn2+ has been shown to cause neurodegeneration. Employing real-time Newport Green fluorescence imaging of extracellular Zn2+, we found that 3-NPA (10-100 microM) caused a concentration-dependent increase in the concentration of extracellular Zn2+ ([Zn2+]o) in acute rat hippocampus slices. This increase in [Zn2+]o was abolished by 10 mM CaEDTA. The increase of [Zn2+]o was also accompanied by a rapid increase of cytoplasmic-free Zn2+ concentration ([Zn2+]i). The induction of Zn2+ release by 3-MPA in hippocampus slices points to a potential mechanism by which 3-NPA might induce neurodegeneration.

• Authors: Guo Wei, Christopher J Hough, John M Sarvey
• Journal: Neuroscience letters (Neurosci Lett) Vol. 370 Issue 2-3 Pg. 118-22 (Nov 11 2004) ISSN: 0304-3940 [Print] Ireland
• PMID: 15488306 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitro Compounds
• Propionates
• Edetic Acid
• Succinate Dehydrogenase
• Zinc
• 3-nitropropionic acid

Topics

• Animals
• Dose-Response Relationship, Drug
• Drug Interactions
• Edetic Acid (pharmacology)
• Extracellular Space (drug effects)
• Hippocampus (drug effects, metabolism)
• In Vitro Techniques
• Microscopy, Fluorescence (methods)
• Nitro Compounds
• Propionates (pharmacology)
• Rats
• Succinate Dehydrogenase (antagonists & inhibitors)
• Time Factors
• Zinc (metabolism)