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PMID:11906213

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Citation

Mellström, B, Ceña, V, Lamas, M, Perales, C, Gonzalez, C and Naranjo, JR (2002) Gas1 is induced during and participates in excitotoxic neuronal death. Mol. Cell. Neurosci. 19:417-29

Abstract

We have performed differential screening to identify genes participating in NMDA-induced neuronal death. The gas1 (growth arrest-specific gene 1) gene, whose product is known to inhibit cell cycle progression, was induced in cultured corticohippocampal neurons committed to die after a brief exposure to NMDA. Overexpression of Gas1 in cultured hippocampal neurons and in human neuroblastoma NB69 cells produced a marked reduction in the number of viable cells. Furthermore, gas1 antisense oligodeoxynucleotide or antisense mRNA protected hippocampal neurons or NB69 cells from neuronal death. Importantly, Gas1-induced neuronal death was attenuated by coexpression of the human Bcl-2 protein or the baculoviral caspase inhibitor OpIAP2. While Gas1 does not directly interact with Bcl-2, OpIAP2 coimmunoprecipitates with Gas1. In addition, induction of gas1 also occurred in rat brain in two models of excitotoxicity: delayed neuronal death after intraperitoneal kainate injection and neuronal death in hippocampal slices after ischemia. These results indicate that Gas1 is induced by activation of glutamate receptors and is part of the gene expression program directing neuronal death after mild excitotoxic insults.

Links

PubMed Online version:10.1006/mcne.2001.1092

Keywords

Amino Acid Chloromethyl Ketones/pharmacology; Animals; Caspases/antagonists & inhibitors; Cell Cycle Proteins; Cell Death/drug effects; Cell Death/physiology; Cysteine Proteinase Inhibitors/pharmacology; Enzyme Inhibitors/pharmacology; Excitatory Amino Acid Agonists/pharmacology; G0 Phase/physiology; GPI-Linked Proteins; Gene Expression/physiology; Humans; Membrane Proteins/genetics; Membrane Proteins/metabolism; N-Methylaspartate/pharmacology; Neuroblastoma; Neurons/cytology; Neurons/physiology; Neurotoxins/pharmacology; Proto-Oncogene Proteins c-bcl-2/genetics; RNA, Antisense; RNA, Messenger/analysis; Rats; Staurosporine/pharmacology; Tumor Cells, Cultured

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:GAS1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q62210

F

Seeded From UniProt

complete

MOUSE:GAS1

located_in

GO:0016020: membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GAS1

acts_upstream_of_or_within

GO:0012501: programmed cell death

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GAS1

acts_upstream_of_or_within

GO:0051726: regulation of cell cycle

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BIRC2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q01721

F

Seeded From UniProt

complete


See also

References

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