title: Glucose deprivation stimulates Cu(2+) toxicity in cultured cerebellar granule neurons and Cu(2+)-dependent zinc release.
abstract: Copper chloride (0.01mM, 2h) did not have significant influence on the survival of cerebellar granule neurons (CGNs) incubated in balanced salt solution. However, CuCl2 caused severe neuronal damage by glucose deprivation (GD). The glutamate NMDA-receptors blocker MK-801 partially and antioxidant N-acetyl-l-cysteine (NAC) or Zn(2+) chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) almost entirely protected CGNs from this toxic effect. Measurements of intracellular calcium ions using Fluo-4 AM, or zinc ions with FluoZin-3 AM demonstrated that 1 h-exposure to GD induced intensive increase of Fluo-4 but not FluoZin-3 fluorescence in neurons. The supplementation of solution with CuCl2 caused an increase of FluoZin-3, Fluo-4 and CellROX Green (reactive oxygen species probe) fluorescence by GD. The stimulation of Fluo-4 but not FluoZin-3 fluorescence by copper could be prevented partially by MK-801 and as well as CellROX Green fluorescence by NAC at GD. This data imply that during GD copper ions induce intense displacement zinc ions from intracellular stores, in addition free radical production, glutamate release and Ca(2+) overload of CGNs, that causes death of neurons as a result.
authors.affiliation: Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, 119991 Moscow, Russia; Research Center of Neurology, 125367 Moscow, Russia. Electronic address: isaev@genebee.msu.ru.
authors.forename: Nickolay K
authors.initials: NK
authors.lastname: Isaev
authors.affiliation: Research Center of Neurology, 125367 Moscow, Russia.
authors.forename: Elisaveta E
authors.initials: EE
authors.lastname: Genrikhs
authors.affiliation: Research Center of Neurology, 125367 Moscow, Russia.
authors.forename: Olga P
authors.initials: OP
authors.lastname: Aleksandrova
authors.affiliation: Research Center of Neurology, 125367 Moscow, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Zelenova
authors.affiliation: Research Center of Neurology, 125367 Moscow, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Stelmashook
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D015032:Zinc / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D003300:Copper; D005947:Glucose; D015032:Zinc; C029892:cupric chloride; D002118:Calcium
keywords: Calcium; Cerebellar granule neurons; Copper; Glucose deprivation; Glutamate; Oxidative stress; Zinc