Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Cell calcium (Edinburgh), 2010-03, Vol.47 (3), p.287-296

Erscheinungsjahr

2010

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• The neurotoxin b-N-oxalyl-l-a,b-diaminopropionic acid (l-b-ODAP) is an l-glutamate analogue at a-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-b-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-b-ODAP. Our data demonstrate increased mitochondrial Ca2+ loading and hyperpolarization of the mitochondrial membrane potential (I[Dot] m), which was specific for l-b-ODAP and not observed with l-glutamate. We conclude that l-b-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.