Mitochondrial Na+/Ca2+ exchanger, a new target for neuroprotection in rat hippocampal slices.
We tested here the hypothesis that the pharmacological modulation of the mitochondrial Na(+)/Ca(2+) exchanger (mNCX) could be a new neuroprotective strategy to rescue stressed vulnerable neurons from death. We used rat hippocampal slices incubated with veratridine to cause neuronal death through a mechanism involving Na(+) and Ca(2+) overload. CGP37157 (CGP), an inhibitor of the mNCX, rescued veratridine vulnerable neurons from death, showing an EC(50) of 5 μM. This neuroprotection was associated to mitigation of veratridine-elicited overproduction of free radicals and to inhibition of the p38 MAPK-linked apoptotic pathway. These results suggest that the mNCX could become a new target to develop compounds with potential therapeutic neuroprotective actions in neurodegenerative diseases.
Nicolau
Santos M
SM
Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
Egea
Javier
J
López
Manuela G
MG
García
Antonio G
AG
D000818:Animals; D002998:Clonazepam / Q000031:analogs & derivatives* / Q000494:pharmacology; D019610:Cytoprotection; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013841:Thiazepines / Q000494:pharmacology*; D014701:Veratridine / Q000633:toxicity
D018696:Neuroprotective Agents; D019831:Sodium-Calcium Exchanger; D013841:Thiazepines; D002998:Clonazepam; D014701:Veratridine; C079032:CGP 37157