RESEARCH: Chemical pathways involved in lathyrism

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Lathyrism has symptoms very similar to uncomplicated

HSP--spasticity and weakness in the legs. It is

caused by eating a plant during drought conditions in

India. This article describes research into the

chemical pathway involved in this disorder.

Mark

In vitro activation of protein kinase C by

beta-N-oxalyl-L-alpha,beta-diaminopropionic acid, the

Lathyrus sativus neurotoxin.

Singh MR, Pratap Rudra MP, Rao SL, Singh SS.

Department of Biochemistry, Osmania University,

Hyderabad, India.

Beta-N-oxalyl-L-alpha,beta-diaminopropionic acid

(L-ODAP) toxicity has been associated with lathyrism;

a spastic paraparesis caused by excessive dietary

intake of the pulse Lathyrus sativus. We investigated

the effect of Lathyrus neurotoxin L-ODAP on protein

kinase C (PKC) activity under in vitro conditions.

L-ODAP activated phosphorylation activity of purified

chick brain PKC. Both lysine-rich (histone III-S) and

arginine-rich (protamine sulfate) substrate

phosphorylation was enhanced in the presence of

L-ODAP. The activation is concentration dependent, and

maximal activation is observed at 100 microM

concentration. Protamine sulfate phosphorylation was

enhanced by 47%, whereas histone III-S phosphorylation

was enhanced by 50% over PS/PDBu/Ca2+ dependent

activity. The nontoxic D-isomer (D-ODAP) did not

affect both histone III-S and protamine sulfate

phosphorylation activity. These results indicate that

L-ODAP taken up by neuronal cells could also

contribute to PKC activation and so be associated with

toxicity.

SOURCE: Neurochem Res. 2004 Jul;29(7):1343-8.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5202763 & dopt=Abstract