Article

The stress protein response in cultured neurons: characterization and evidence for a protective role in excitotoxicity.

Department of Neurology, University of California, San Francisco 94143.
Neuron (Impact Factor: 15.98). 01/1992; 7(6):1053-60. DOI: 10.1016/0896-6273(91)90349-5
Source: PubMed

ABSTRACT We used purified cultures of cerebellar granule cells to investigate the possible protective role of stress proteins in an in vitro model of excitotoxicity. Initial experiments used one- and two-dimensional polyacrylamide gel electrophoresis to confirm the induction of typical stress protein size classes by heat shock, sodium arsenite, and the calcium ionophore A23187. Immunoblot analysis and immunocytochemistry verified the expression of the highly inducible 72 kd heat shock protein (HSP72). Granule cell cultures exposed to glutamate showed evidence of cellular injury that was prevented by the noncompetitive NMDA antagonist MK-801, yet glutamate did not induce a detectable stress protein response. Nonetheless, preinduction of heat shock proteins was associated with protection from toxic concentrations of glutamate. These results imply that the HSP72 expression observed in in vivo models of excitotoxicity may not be directly related to the effects of excitatory amino acids. However, the ability of stress protein induction to protect against injury from glutamate may offer a novel approach toward ameliorating damage from excitotoxins.

0 Followers
 · 
48 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Arsenate is an environmental pollutant which contaminates the drinking water of millions of people worldwide. Numerous in vitro studies have investigated the toxicity of arsenate for a large number of different cell types. However, despite the known neurotoxic potential of arsenicals, little is known so far about the consequences of an exposure of neurons to arsenate. To investigate acute effects of arsenate on the viability and the glutathione (GSH) metabolism of neurons, we have exposed primary rat cerebellar granule neuron cultures to arsenate. Incubation of neurons for up to 6 h with arsenate in concentrations of up to 10 mM did not acutely compromise the cell viability, although the cells accumulated substantial amounts of arsenate. However, exposure to arsenate caused a time- and concentration-dependent increase in the export of GSH from viable neurons with significant effects observed for arsenate in concentrations above 0.3 mM. The arsenate-induced stimulation of GSH export was abolished upon removal of arsenate and completely prevented by MK571, an inhibitor of the multidrug resistance protein 1. These results demonstrate that arsenate is not acutely toxic to neurons but can affect the neuronal GSH metabolism by stimulating GSH export.
    Neurochemical Research 12/2014; 40(3). DOI:10.1007/s11064-014-1501-1 · 2.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To prove the sensitizing effect of Tween80 to heat on the thermotolerance and expression of Heat shock protein(HSP) 70 in the human ovarian cancer cell line SKOV-3. Methods: The proliferation rate of cell was detected by methyltetrazolium (MTT) assay. The expression of Heat shock protein 70 was detected by immunocytochemical assay. Results: The cells were inhibited and killed after 42℃ hyperthermia firstly. But the cell proliferation rate of the groups reheated was quickened. The inhibition ratio of proliferation of groups treated by the combined treatment of Tween80 and 42℃ hyperthermia is higher than that of the cell of the control groups, the inhibition ratio of cell proliferation rise obviously after reheating compared to the control groups treated by 42℃ hyperthermia simply. After heating for 100mins, the expression of HSP70 of the experiment groups is weaker than groups treated by 42℃ hyperthermia simply after 8 hours. With increase of the concentration of Tween80, the inhibition effect of HSP70 expression is obvious. Conclusions: Hyperthermia of 42℃ for 100 mins can induce thermotolerance of the human ovarian cancer cell line SKOV-3. Tween80 may inhibit thermotolerance of the cell and has a sensitizing effect on SKOV-3 treated by 42℃ hyperthermia. Tumor hyperthermia is a method which advances the temperature of body and/or tumor tissue by kinds of ways and treats malignant tumor by hyperthermia and secondary effect. Due to the needed therapy temperature is high, usually reached 40℃-43℃[1], it induces high mortality of tumor cell, and causes the damnification of human normal cell simultaneously. Otherwise, thermotolerance always accompanied by hyperthermia, which reduces its efficacy. Thermotolerance is a characteristic of cells, when they are heated beforehand or continually with nonfatal thermal dose their sensitivity descends. In order to resolve the above issues, we try to search for a kind of sensitizing agent of hyperthermia which can debase the temperature of hyperthermia and increase the effect. The experiment wants to let Tween80 combined with 42℃ hyperthermia to act on human ovarian cancer cell line SKOV-3 and investigate the effect of the thermotolerance and expression of HSP70.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The last decade has witnessed a mammoth progress in the area of brain ageing. Recent gene profiling and brain imaging techniques have made it possible to explore the dark areas of ageing neurons in a new molecular perspective. Many conserved pathways and cellular and molecular mechanisms particularly nuclear mitochondrial molecular interactions are known now. Disruptions in mitochondrial function and reduction in cellular antioxidative and immunoproteins contribute to generation of reactive oxygen species (ROS) which leads to deteriorated adult neurogenesis, reduced white matter and compromised neural plasticity. The overall deteriorated structure and function of neurons is manifested in form of cognitive decline and prolonged neurodegenerative disorders. Dietary restrictions (DR), physical and mental activities however have been shown to counter these ailments. However more precise molecular dynamics at protein levels is still debatable which is the future task for neuroscientists.
    Annals of Neurosciences 10/2012; 19(4):177-182. DOI:10.5214/ans.0972.7531.190410