In vitro activation of protein kinase C by beta-N-oxalyl-L-alpha,beta-diaminopropionic acid, the Lathyrus sativus neurotoxin.

Abstract

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.