In vitro activation of protein kinase C by beta-N-oxalyl-L-alpha,beta-diaminopropionic acid, the Lathyrus sativus neurotoxin.
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.
Singh
M Raghuveer
MR
Department of Biochemistry, Osmania University, Hyderabad, India.
Pratap Rudra
M P
MP
Rao
S L N
SL
Singh
Surya S
SS
D000599:Amino Acids, Diamino / Q000138:chemical synthesis / Q000494:pharmacology*; D004789:Enzyme Activation; D006657:Histones / Q000378:metabolism; D007700:Kinetics; D008823:Micelles; D009498:Neurotoxins / Q000494:pharmacology*; D010766:Phosphorylation; D011479:Protamines / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*
D000599:Amino Acids, Diamino; D006657:Histones; D008823:Micelles; D009498:Neurotoxins; D011479:Protamines; C100126:oxalyldiaminopropionic acid; D011493:Protein Kinase C