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L-beta-ODAP alters mitochondrial Ca2+ handling as an early event in excitotoxicity

Marijke Van Moorhem1, Elke Decrock, Evelyne Coussee

  • 1Department of Basic Medical Sciences-Physiology Group, Faculty of Medicine and Health Sciences, De Pintelaan 185 (Block B, 3th Floor), Ghent University, B-9000 Ghent, Belgium.

Cell Calcium
|February 5, 2010
PubMed

Insights

The neurotoxin beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (L-beta-ODAP) disrupts cellular calcium handling in neurons. This excitotoxic effect, linked to neurolathyrism, involves endoplasmic reticulum-mitochondrial signaling disruption.

Area of Science:

  • Neuroscience
  • Toxicology
  • Cell Biology

Background:

  • Beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (L-beta-ODAP), found in Lathyrus sativus seeds, is a suspected cause of neurolathyrism.
  • L-beta-ODAP acts as an excitotoxic substance by mimicking glutamate at AMPA/kainate receptors.
  • Excitotoxicity involves disrupted intracellular calcium (Ca2+) homeostasis, affecting stores like the endoplasmic reticulum (ER) and mitochondria.

Purpose of the Study:

  • To investigate how L-beta-ODAP affects cellular Ca2+ handling in neuronal cells.
  • To elucidate the specific mechanisms underlying L-beta-ODAP's excitotoxicity.

Main Methods:

  • Utilized aequorin and other Ca2+ indicators in N2a neuroblastoma cells.
  • Examined alterations in cellular Ca2+ handling following 24-hour exposure to L-beta-ODAP.
  • Compared L-beta-ODAP effects with those of L-glutamate.

Main Results:

  • Observed increased mitochondrial Ca2+ loading in cells exposed to L-beta-ODAP.
  • Detected hyperpolarization of the mitochondrial membrane potential (Psi(m)) specifically with L-beta-ODAP exposure.
  • These effects were not replicated with L-glutamate treatment.

Conclusions:

  • L-beta-ODAP disrupts the endoplasmic reticulum-mitochondrial Ca2+ signaling axis.
  • This disruption increases neuronal vulnerability to excitotoxic effects and subsequent cell death.
  • The findings provide mechanistic insights into L-beta-ODAP-induced neurotoxicity.

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