Kainic acid induced excitotoxicity and cfos expression in fibroblasts transfected with glutamate receptor subunit, GluR1.
Glutamate receptors participate in the majority of fast excitatory neurotransmission in the mammalian brain. Excessive excitation of these receptors has been linked to neuronal dysfunction and death through a process termed excitotoxicity. In this study we demonstrate that transfection of a single non-NMDA glutamate receptor subunit, GluR1, into cultured fibroblasts is sufficient to confer kainic acid mediated excitotoxicity similar to that seen in neuronal cells. Death of transfected cells requires at least 24 h of continuous exposure to kainic acid and can be blocked with a glutamate receptor antagonist. Also, the induction of protooncogene cfos transcripts occurs 30 min following kainic acid administration, and Fos protein accumulated in the nucleus within 90 min. These observations suggest that the signaling system(s) required to initiate gene expression and kainic acid excitotoxicity from a neuronal ionotropic receptor to the nucleus is present in these nonneuronal cells. Finally, antibodies prepared to amino acids 185-449 of GluR1 are demonstrated to be useful for fluorescence-activated sorting of live cells transfected with a GluR1 expression vector. This supports the conclusion that this region of the protein is located extracellularly.
Gahring
L C
LC
Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center, Salt Lake City, Utah 84148, USA.
Cauley
K
K
Rogers
S W
SW
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D007608:Kainic Acid / Q000633:toxicity*; D007736:Kynurenic Acid / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics*; D014162:Transfection
D018691:Excitatory Amino Acid Antagonists; D007608:Kainic Acid; D007736:Kynurenic Acid; D016760:Proto-Oncogene Proteins c-fos; D018091:Receptors, AMPA