Slowly triggered excitotoxicity occurs by necrosis in cortical cultures

Alterations of Extracellular Calcium Elicit Selective Modes of Cell Death and Protease Activation in SH‐SY5Y Human Neuroblastoma Cells

“…Continued activation of these receptors leads to persistent Ca2' entry and resultant cell death. Although there may be an apoptotic component, evidence suggests that cell death from excitatory amino acids is primarily necrotic (Ikeda et al, 1996;Gwag et al, 1997) and attributable to increased intracellular Ca2+ levels (Mattson, 1990;Clementi et al, 1996). An interesting result of this study is that the cysteine proteases caspase-3 and calpain were selectively activated by the alterations in Ca2+e.…”

“…However, the mode of cell death and direction of change in Ca2fi differ among cell types McConkey and Orrenius, 1997). An overload of Ca2+, contributes directly to excitotoxicity-induced necrosis (Munir et a]., 1995;Ikeda et al, 1996;Gwag et al, 1997) but can also lead to apoptosis (Furuya et al, 1994;Zhu and Loh, 1995) depending on the cell type. Chelation of extracellular Ca" (Ca",) protects against apoptosis induced by specific agents in thymocytes (McConkey et al, 1989;Story …”

Tissue inhibitor of metalloproteinases-3 (TIMP-3) expression is increased during serum deprivation-induced neuronal apoptosis in vitro and in the G93A mouse model of amyotrophic lateral sclerosis: A potential modulator of Fas-mediated apoptosis

“…Quantitative 2-dimensional analysis of proteins sensitive to serum deprivation in neuron-rich cortical cell cultures Neuron-rich cortical cell cultures deprived of serum undergo widespread neuronal apoptosis over 24 h that depends on protein synthesis (Gwag et al, 1997). Delayed administration of cycloheximide, a protein synthesis inhibitor, inhibited serum deprivationinduced neuronal apoptosis (SDIA) by N 60% for up to 8 h after serum deprivation (data not shown).…”

“…However, levels of TIMP-3 were not altered 1-8 h after exposure of cortical cell cultures to Fe 2+ or NMDA (Fig. 2B), which caused neuronal necrosis (Gwag et al, 1997;Won et al, 2000), suggesting that TIMP-3 was increased during the course of neuronal apoptosis, but not necrosis. Immunoreactivity to TIMP-3 was present throughout neuronal cell bodies and processes in serum-containing cultures, and its intensity was markedly increased in cell bodies 8 h after serum deprivation (Fig.…”

Nuclear factor kappa B-mediated kainate neurotoxicity in the rat and hamster hippocampus

“…35 It becomes evident that necrosis is a predominant pattern of excitotoxic neuronal death according to morphology, biochemical events and interventional criteria. 18 Systemic injections of kainate into the adult rat also induced degeneration of hippocampal neurons exclusively via necrosis (q99%), marked by swelling of the cell body and mitochondria, rapid collapse of the plasma membrane and scattering of nuclear chromatin (Huh K. and Sohn S., unpublished observation). Therefore, activation of NF-kB appears to promote the propagation of excitotoxic neuronal necrosis, whereas it may counteract the apoptosis transduction pathway, as shown previously.…”