Blocked gap junctional coupling increases glutamate-induced neurotoxicity in neuron-astrocyte co-cultures.

Content Provider	Semantic Scholar
Author	Ozog, Mark A. Siushansian, Ramin
Copyright Year	2002
Abstract	Gap junctional communication is likely one means by which neurons can endure glutamate cytotoxicity associated with CNS insults (i.e. ischemia). To examine this neuroprotective role of gap junctions, we employed gap junctional blockers to neuronal and astrocytic co-cultures during exposure to a high concentration of extracellular glutamate. Co-cultures were treated with the blocking agents carbenoxolone (CBX; 25 microM), 18alpha-glycyrrhetinic acid (AGA; 10 microM), vehicle or the inactive blocking analogue glycyrrhizic acid (GZA; 25 microM). Twenty-four hours following the insult, cell mortality was analyzed and quantified by the release of lactate dehydrogenase (LDH) into the media, the cells' inability to exclude propidium iodide, and terminal dUTP nick end labeling (TUNEL). Measurement of LDH release revealed that the glutamate insult was detrimental to the co-cultures when gap junctions were blocked with CBX and AGA. Based on propidium iodide and TUNEL labeling, the glutamate insult caused significant cell death compared to sham vehicle and mortality was amplified in the presence of CBX and AGA. Since blockers were not themselves toxic and did not affect astrocytic uptake of glutamate, it is likely that blocked gap junctions lead to the increased glutamate cytotoxicity. These findings support the hypothesis that gap junctions play a neuroprotective role against glutamate cytotoxicity.
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Alternate Webpage(s)	http://jnen.oxfordjournals.org/content/jnen/61/2/132.full.pdf
PubMed reference number	11855382v1
Volume Number	61
Issue Number	2
Journal	Journal of neuropathology and experimental neurology
Language	English
Access Restriction	Open
Subject Keyword	Analog Astrocytes CBX1 gene Carbenoxolone Cell Death Cessation of life Coculture Techniques Codependency (Psychology) Gap Junctions Glutamic Acid Glycyrrhetinic acid Glycyrrhizic Acid In Situ Nick-End Labeling Inactive - Biochemical Activity Level Iodides Lactate Dehydrogenase Lactic acid Neurons Neurotoxicity Syndromes Propidium Iodide Thioctic Acid childhood central nervous system germ cell tumor deoxyuridine triphosphate polyethylene glycol-glutaminase-asparaginase
Content Type	Text
Resource Type	Article