The mitochondrial toxin, 3-nitropropionic acid, induces extracellular Zn2+ accumulation in rat hippocampus slices.
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.
Department of Pharmacology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA. gwei1@jhmi.edu
Guo
G
Wei
Christopher J
CJ
Hough
John M
JM
Sarvey
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004492:Edetic Acid / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008856:Microscopy, Fluorescence / Q000379:methods; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors*; D013997:Time Factors; D015032:Zinc / Q000378:metabolism*
D009574:Nitro Compounds; D011422:Propionates; D004492:Edetic Acid; D013385:Succinate Dehydrogenase; D015032:Zinc; C015392:3-nitropropionic acid