title: Excitotoxic potential of exogenous ferritin and apoferritin: changes in ambient level of glutamate and synaptic vesicle acidification in brain nerve terminals.
abstract: Ferritin, an iron storage protein, is present in the serum and cerebrospinal fluid, has receptors on the cell surface, able to penetrate the brain-blood barrier, can be secreted from the cells, and leaks from destroyed cell in insult and brain trauma. The effect of exogenous ferritin on the key characteristic of glutamatergic neurotransmission was assessed in rat brain nerve terminals (synaptosomes). Exogenous ferritin (80 μg/ml, iron content 0.7%) significantly increased the ambient level of L-[(14)C]glutamate (0.200±0.015 versus 0.368±0.016 nmol/mg of protein) and endogenous glutamate (fluorimetric glutamate dehydrogenase assay) in the nerve terminals. This increase was not a result of augmentation of tonic release because the velocity of tonic release of L-[(14)C]glutamate was not changed significantly in ferritin-treated synaptosomes as compared to the control. Ferritin caused a decrease in synaptic vesicle acidification that was shown using fluorescent dye acridine orange. Iron-dependence of the effects of ferritin was analyzed with apoferritin (0.0025% residual iron). Apoferritin weakly affected the proton electrochemical gradient of synaptic vesicles but increased the ambient level and decreased the initial velocity of uptake of L-[(14)C]glutamate by synaptosomes, nevertheless these effects were ~30% lesser than those caused by ferritin. Exogenous ferritin can provoke the development of excitotoxicity increasing the ambient level of glutamate and lowering synaptic vesicle acidification and glutamate uptake in the nerve terminals, however these effects are not completely iron-dependent. Thus, in the CNS exogenous ferritin can act as a modulator of glutamate homeostasis in iron-dependent and iron-independent manner.
authors: The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Street, Kiev 01601, Ukraine.
authors: N
authors: N
authors: Krisanova
authors: The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Street, Kiev 01601, Ukraine.
authors: R
authors: R
authors: Sivko
authors: The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Street, Kiev 01601, Ukraine.
authors: L
authors: L
authors: Kasatkina
authors: The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Street, Kiev 01601, Ukraine.
authors: A
authors: A
authors: Borуsov
authors: The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Street, Kiev 01601, Ukraine. Electronic address: tborisov@biochem.kiev.ua.
authors: T
authors: T
authors: Borisova
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008564:Membrane Potentials; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011522:Protons; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D011522:Protons; D018698:Glutamic Acid; D001052:Apoferritins
keywords: Ambient level; Apoferritin; Ferritin; Glutamate; Rat brain nerve terminals; Synaptic vesicle acidification; Uptake