Mitochondrial impairment induces excitotoxic death in cerebellar granule cells.
A close relationship links mitochondria to cell death with mitochondrial function-impairment considered a major biochemical event in the process of both apoptosis and necrosis. We have used different inhibitors of oxidative phosphorylation, i.e. mitochondrial respiratory chain and ATP synthesis inhibitors, and an uncoupler to investigate the mode of cell death caused by these compounds in cerebellar granule cells. This study shows that in cultured cerebellar granule cells either oxidative phosphorylation inhibitors or uncoupler induce an excitotoxic-like reaction which is mediated by activation of NMDA receptors and is likely due to the release of glutamate. Consistently, survival may occur if the toxic action of glutamate is prevented.
Bobba
Antonella
A
Istituto di Biomembrane e Bioenergetica, CNR, I-70126 Bari, Italy. csmmab03@area.ba.cnr.it
Atlante
Anna
A
Azzariti
Amalia
A
Sgaramella
Giuseppe
G
Calissano
Pietro
P
Marra
Ersilia
E
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D000255:Adenosine Triphosphate