l-β-ODAP alters mitochondrial Ca2+ handling as an early event in excitotoxicity.

Autor: Van Moorhem, Marijke, Decrock, Elke, Coussee, Evelyne, Faes, Liesbeth, De Vuyst, Elke, Vranckx, Katleen, De Bock, Marijke, Wang, Nan, D’Herde, Katharina, Lambein, Fernand, Callewaert, Geert, Leybaert, Luc
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Zdroj: Cell Calcium; Mar2010, Vol. 47 Issue 3, p287-296, 10p
Abstrakt: Abstract: The neurotoxin β-N-oxalyl-l-α,β-diaminopropionic acid (l-β-ODAP) is an l-glutamate analogue at α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptors in neurons and therefore acts as an excitotoxic substance. Chronic exposure to l-β-ODAP present in Lathyrus sativus L. (L. sativus) seeds is proposed as the cause of the neurodegenerative disease neurolathyrism, but the mechanism of its action has not been conclusively identified. A key factor in excitotoxic neuronal cell death is a disturbance of the intracellular Ca2+ homeostasis, including changes in the capacity of intracellular Ca2+ stores like the endoplasmic reticulum (ER) or mitochondria. In this study, aequorin and other Ca2+ indicators were used in N2a neuroblastoma cells to investigate alterations of cellular Ca2+ handling after 24h exposure to l-β-ODAP. Our data demonstrate increased mitochondrial Ca2+ loading and hyperpolarization of the mitochondrial membrane potential (Ψ m), which was specific for l-β-ODAP and not observed with l-glutamate. We conclude that l-β-ODAP disturbs the ER–mitochondrial Ca2+ signaling axis and thereby renders the cells more vulnerable to its excitotoxic effects that ultimately will lead to cell death. [Copyright &y& Elsevier]
Databáze: Supplemental Index
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