Attenuation of neurotoxicity following anoxia or glutamate receptor activation in EGF- and hippocampal extract-treated neuronal cultures

Pauwels, Petrus J.; Assouw, Harrie P. van; Leysen, Josée E.

doi:10.1016/0898-6568(89)90019-3

Cited by 29 publications

(15 citation statements)

References 24 publications

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“…Trophic factors are intriguing in their ability to offer protection from several toxic states such as anoxia (Maiese et al, 1993a), KCN (Pauwels et al, 1989), hypoglycemia (Cheng and Mattson, 1991), and NO (Maiese et al, 1993a). Yet, the PKC pathway appears to also play a role in the cellular mechanisms regulated by growth factors.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotection by Peptide Growth Factors against Anoxia and Nitric Oxide Toxicity Requires Modulation of Protein Kinase C

Maiese

Boccone

1995

J Cereb Blood Flow Metab

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Summary: Basic fibroblast growth factor (bFGF) and epi dermal growth factor (EGF) are neuroprotective during anoxia and nitric oxide (NO) toxicity. Signal transduction systems that modulate protein kinase C (PKC) also can modulate the toxic effects of anoxia and NO. We there fore examined whether PKC was involved in the protec tive effects of bFGF and EGF during anoxia and NO toxicity. Down-regulation or inhibition of PKC activity before anoxia or NO exposure prevented hippocampal neuronal degeneration. Yet, this protective effect of inhi bition of PKC activity was not present with the coadmin istration of growth factors. Combined inhibition of PKC activity and application of bFGF or EGF lessened the protective mechanisms of the growth factors. In addition, the protective ability of the growth factors was lost during anoxia and NO exposure with the activation of PKC, Peptide growth factors are increasingly being linked to the neurodegenerative effects of cerebral ischemia. In animal models, increased expression of basic fibroblast growth factor (bFGF) has been documented during both focal (Kumon et aI., 1993) and global (Takami et aI., 1992) models of cerebral ischemia. Administration of some trophic factors, such as insulin-like growth factor (Guan et aI., 1993) and transforming growth factor-Bl (Gross et aI., 1993), can reduce or limit the extent of cerebral

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Section: Discussionmentioning

confidence: 99%

Neuroprotection by Peptide Growth Factors against Anoxia and Nitric Oxide Toxicity Requires Modulation of Protein Kinase C

Maiese

Boccone

1995

J Cereb Blood Flow Metab

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“…The loss of EGF-R in the brain might make it more susceptible to such injury. Numerous investigators have demonstrated neuroprotective effects of EGF-R-activating ligands in models of hypoxia-ischemia or excitotoxicity in vitro (Pauwels et al, 1989;Abe and Saito, 1992;Maiese et al, 1993). It is not yet known whether these protective effects are mediated directly via neuronallyexpressed receptors or indirectly via glia.…”

Section: Potential Mechanisms For Neuronal Degeneration In Egf-r ؊/؊ mentioning

confidence: 98%

Abnormal astrocyte development and neuronal death in mice lacking the epidermal growth factor receptor

et al. 1998

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Stimulation of the epidermal growth factor receptor (EGF-R) produces numerous effects on central nervous system (CNS) cells in vitro including neuronal survival and differentiation, astrocyte proliferation and the proliferation of multipotent progenitors. However, the in vivo role of EGF-R is less well understood. In the present study, we demonstrate that EGF-R null mice generated on a 129Sv/J Swiss Black background undergo focal but massive degeneration the olfactory bulb, piriform cortex, neocortex, and thalamus between postnatal days 5 and 8 which is due, at least in part, to apoptosis. Some of the neuronal populations that degenerate do not normally express EGF-R, indicating an indirect mechanism of neuronal death. There were also delays in GFAP expression within the glia limitans and within structures outside the germinal zones in early postnatal ages. At or just prior to the onset of the degeneration, however, there was an increase in GFAP expression in these areas. The brains of EGF-R (-/-) animals were smaller but cytoarchitecturally normal at birth and neuronal populations appeared to be intact, including striatal GABAergic and midbrain dopaminergic neurons which have previously been shown to express EGF-R. Multipotent progenitors and astrocytes derived from EGF-R (-/-) mice were capable of proliferating in response to FGF-2. These data demonstrate that EGF-R expression is critical for the maintenance of large portions of the postnatal mouse forebrain as well as the normal development of astrocytes.

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“…For example, cyanide can raise extracellular glutamate levels (5,6), increase glutamate-triggered intracellular Ca 2ϩ elevations in neurons (7,8), and potentiate glutamate toxicity (7,9). Moreover, specific inhibitors of Nmethyl-D-aspartate (NMDA) 1 receptors can inhibit cyanide-induced Ca 2ϩ influx in neurons (7,10,11) as well as neurotoxicity (12)(13)(14).…”

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confidence: 99%

Subunit-specific Interactions of Cyanide with the N-Methyl-d-aspartate Receptor

Arden

Sinor

Potthoff

et al. 1998

Journal of Biological Chemistry

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Cyanide is a mitochondrial poison that adversely affects cellular respiration by inhibiting the reoxidation of cytochrome a 3 by molecular oxygen, thereby obstructing the electron transport chain and oxidative phosphorylation (1). Cytochrome a 3 and cytochrome a form the cytochrome c oxidase complex, which is the terminal enzyme in the electron transport chain. Transferring electrons to oxygen, cytochrome c oxidase is the cellular respiratory component responsible for the critical need for oxygen. Thus, cyanide intoxication in cells is akin to oxygen starvation. In neuronal systems, cyanide treatment has been a widely used model of hypoxia (2-4), particularly in relation to excitotoxic processes. For example, cyanide can raise extracellular glutamate levels (5, 6), increase glutamate-triggered intracellular Ca 2ϩ elevations in neurons (7,8), and potentiate glutamate toxicity (7, 9). Moreover, specific inhibitors of Nmethyl-D-aspartate (NMDA) 1 receptors can inhibit cyanide-induced Ca 2ϩ influx in neurons (7, 10, 11) as well as neurotoxicity (12-14).Interestingly, a direct interaction between cyanide and the NMDA receptor has recently been demonstrated. Cyanide treatment of cultured rat hippocampal or cerebellar neurons potentiated NMDA-induced physiological responses, including single channel activity in excised outside-out membrane patches (15, 16). However, the precise site of action of cyanide at the receptor remained to be elucidated. In the present investigations we have evaluated the possible interaction of KCN on the NMDA receptor redox modulatory sites (17). Via these sites, disulfide-reducing agents such as dithiothreitol (DTT; see Refs. 17 and 18), dihydrolipoic acid (19), or tris(carboxyethyl)phosphine (20) enhance NMDA receptor-mediated physiological responses, whereas thiol-containing oxidants (21, 22), reactive quinones (23, 24), or oxygen-derived free radicals (25,26) can reverse the effects of reductants or depress native responses. Cyanide has well established properties as a disulfide reducing agent in many preparations (27)(28)(29)(30), and thus an effect on the NMDA thiol-sensitive sites would not be surprising. Nonetheless, the experiments described here demonstrate that cyanide can be used to distinguish between different NMDA receptor subtypes by producing either a potentiation or a depression of the physiological responses mediated by this ligand-gated ion channel. EXPERIMENTAL PROCEDURESTissue Culture-Tissue culture and all common reagents were purchased from Sigma, excluding the following: iron-supplemented bovine calf serum, HyClone Laboratories (Logan, UT), and minimal essential medium, Life Technologies, Inc. Chinese hamster ovary cells (CHO-K1; ATTC CCL61) were grown in Ham's F-12 nutrient medium with 10% fetal bovine serum, and 1 mM glutamine (CHO media) in 50-or 200-ml flasks at 37°C in 5% CO 2 . Cells were passaged at a 1:10 dilution at 80% confluency, approximately every 2 days, no more than 30 times. Cerebral cortices were obtained from E-16 Sprague-Dawley C-D rats and dissocia...

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Attenuation of neurotoxicity following anoxia or glutamate receptor activation in EGF- and hippocampal extract-treated neuronal cultures

Cited by 29 publications

References 24 publications

Neuroprotection by Peptide Growth Factors against Anoxia and Nitric Oxide Toxicity Requires Modulation of Protein Kinase C

Neuroprotection by Peptide Growth Factors against Anoxia and Nitric Oxide Toxicity Requires Modulation of Protein Kinase C

Abnormal astrocyte development and neuronal death in mice lacking the epidermal growth factor receptor

Subunit-specific Interactions of Cyanide with the N-Methyl-d-aspartate Receptor

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