Gliotoxic properties of theLathyrus excitotoxinβ-N-oxalyl-l-α,β-diaminopropionic acid (β-l-ODAP)

Bridges, Richard J.; Hatalski, Carolyn G.; Shim, Sung N.; Nunn, Peter B.

doi:10.1016/0006-8993(91)91602-w

Cited by 37 publications

(18 citation statements)

References 35 publications

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“…The physiological relevance of the previously reported p-L-ODAP-induced gliotoxicity is unclear because the concentrations used to produce gliotoxicity (Bridges et al, 1991) were much greater than those required for neuronal toxicity (Weiss et al, 1989). However, the present report that low concentrations of P-L-ODAP are capable of altering GS activity gives further evidence that glia as well as neurons are involved in the response to exogenous insults and provides a more physiological suggestion that astrocytes could be affected in lathyrism.…”

Section: Discussionmentioning

confidence: 60%

“…Specifically, a similar enantiomeric selectivity to the L-isomer of P-ODAP has been shown for the neurotoxic (Nunn et a]., 1987) and gliotoxic (Bridges et al, 1991) effects of P-ODAP. cy-L-ODAP, which was unable to alter GS activity, is also ineffective in the displacement of binding to NMDA and non-NMDA glutamate receptors (Bridges et al, 1989), and is neither acutely nor chronically toxic in rat spinal p-L-ODAP AND ASTROCYTE GLUTAMINE SYNTHETASE cord (Chase et al, 1985).…”

Section: Discussionmentioning

confidence: 90%

“…In synaptosomal studies p-L-ODAP has been shown to enhance glutamate release (Gannon and Terrian, 1989) and inhibit glutamate uptake (Lakshmanan and Padmanaban, 1974;Ross et al, 1985). In addition to the well-established actions of p-L-ODAP on neurons, our laboratory has recently reported a gliotoxic activity of this amino acid (Bridges et al, 1991).…”

Section: Introductionmentioning

confidence: 98%

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Induction of astrocyte glutamine synthetase activity by the lathyrus toxin β‐N‐oxalyl‐L‐α,β‐diaminopropionic acid (β‐L‐ODAP)

Miller

Nunn

Bridges

1993

Glia

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beta-N-Oxalyl-L-alpha,beta-diaminopropionic acid (beta-L-ODAP) is thought to be the causative agent in lathyrism due to its neuroexcitatory and neurotoxic properties. We have recently reported that beta-L-ODAP is also gliotoxic at high concentrations (Bridges et al.: Brain Res 561:262, 1991). Evidence is now presented that low, subgliotoxic concentrations of beta-L-ODAP may alter the ability of astrocytes to regulate glutamate concentrations in the CNS by increasing astrocyte glutamine synthetase activity. When astrocytes cultured from rat cortex were exposed to 100 microM beta-L-ODAP for 24 h, the resulting glutamine synthetase activity was 155% of control levels. This effect was enantiomer- and isomer-specific, dose-dependent, and required protein translation as the induction was blocked with cycloheximide. The effect of beta-L-ODAP on glutamine synthetase was not mimicked by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) or kainate, suggesting that the induction was not transduced solely through activation of cell surface non-N-methyl-D-aspartate (NMDA) glutamate receptors. An intracellular site of action of beta-L-ODAP is proposed because its effect on glutamine synthetase activity could be blocked by the amino acid uptake blocker dihydrokainate.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 98%

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Induction of astrocyte glutamine synthetase activity by the lathyrus toxin β‐N‐oxalyl‐L‐α,β‐diaminopropionic acid (β‐L‐ODAP)

Miller

Nunn

Bridges

1993

Glia

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“…It also exerts some toxicity against those cells that are the 'power house' producing the energy-rich ATP for the neurons. 42 The mitochondria, the intracellular power houses of the cell, seem to be specifically affected. 43 The astrocyte cells normally absorb the glutamate released into the synaptic cleft during neuronal signalling and these glutamate molecules are the normal agents for the excitation at the AMPAreceptors that involves the release of short-lived molecules of nitric oxide (NO).…”

Section: β-Odap Biochemistrymentioning

confidence: 99%

3-N-oxalyl-L-2,3-diaminopropanoic acid, a multifunctional plant metabolite of toxic reputation

Lambein¹,

Kuo²,

Kusama-Eguchi³

et al. 2006

Arkivoc

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3-N-oxalyl-L-2,3-diaminopropanoic acid (β-ODAP ) is a neuroexcitatory non-protein amino acid identified in grass pea (Lathyrus sativus L.) and in ginseng (Panax spp). Its presence in the drought tolerant grass pea is thought to be responsible for the crippling disease neurolathyrism, while in the longevity promoting ginseng it is named dencichine and praised for its haemostatic properties. Some properties of β-ODAP are put in perspective.

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“…The component of L. sativus responsible for corticospinal motor neuron degeneration was identified as early as 1963 13,14 . It is currently known as β-N-oxalyl-L-α,β-diaminopropionic acid (β-ODAP), but was previously known as β-N-oxalylamino-Lalanine (BOAA) 15,16 . Its effects are that of a glutamate (i.e.…”

mentioning

confidence: 99%

Neurolathyrism in Vapniarka: Medical Heroism in a Concentration Camp

Garfinkle

Andermann

Shevell

2011

Can. J. Neurol. Sci.

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Stories abound about the medical abuses that have come to define medicine and the “pseudo”-neurosciences in the Third Reich. Well known are the Nazi program of euthanasia and the neuroscientific publications that arose from it. Nevertheless, during this widespread perversion of medical practice and science, true medical heroics persisted, even in the concentration camps. In December 1942, inmates of Camp Vapniarka began experiencing painful lower extremity muscle cramps, spastic paraparesis, and urinary incontinence. In order to reduce the cost of feeding the 1200, mostly Jewish, inmates of Camp Vapniarka and surreptitiously hasten their deaths, the Nazi-affiliated Romanian officers of the camp had begun feeding them a diet high in Lathyrus sativus. L. sativus is the neurotoxin implicated in neurolathyrism, a degenerative disease of the upper motor neurons. Dr. Arthur Kessler, one of the camp's prisoners, eventually identified the source of the epidemic. Armed with this knowledge, the inmates collectively organized to halt its spread.

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Gliotoxic properties of theLathyrus excitotoxinβ-N-oxalyl-l-α,β-diaminopropionic acid (β-l-ODAP)

Cited by 37 publications

References 35 publications

Induction of astrocyte glutamine synthetase activity by the lathyrus toxin β‐N‐oxalyl‐L‐α,β‐diaminopropionic acid (β‐L‐ODAP)

Induction of astrocyte glutamine synthetase activity by the lathyrus toxin β‐N‐oxalyl‐L‐α,β‐diaminopropionic acid (β‐L‐ODAP)

3-N-oxalyl-L-2,3-diaminopropanoic acid, a multifunctional plant metabolite of toxic reputation

Neurolathyrism in Vapniarka: Medical Heroism in a Concentration Camp

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