Eosinophil-derived neurotoxin and human liver ribonuclease. Identity of structure and linkage of neurotoxicity to nuclease activity.
Eosinophil-derived neurotoxin (EDN) and human liver RNase were found to be indistinguishable from each other but distinct from the pancreatic ribonucleases in their nucleolytic activity on polynucleotides or small defined substrates. Antibodies to EDN and liver RNase showed identical cross-reactivities in assays of nuclease inhibition and in a radioimmunoassay. In each instance, EDN and liver RNase were easily distinguished from bovine or human pancreatic RNase. When injected intrathecally into rabbits, 5-10 micrograms of EDN or liver RNase each was neurotoxic as judged by induction of the Gordon phenomenon. Human pancreatic RNase was less neurotoxic, and up to 20-fold higher levels of bovine pancreatic RNase showed no effect. Treatment of EDN, liver RNase, and eosinophil cationic protein with iodoacetic acid at pH 5.5 resulted in inactivation of their RNase activity and also destroyed their neurotoxicity. EDN conformation was not greatly affected by iodoacetate treatment since interaction of the modified protein with antibodies was only slightly altered. We conclude that RNase activity is necessary but not sufficient to induce neurotoxic action.
Sorrentino
S
S
Department of Biological Chemistry, UCLA School of Medicine 90024.
Glitz
D G
DG
Hamann
K J
KJ
Loegering
D A
DA
Checkel
J L
JL
Gleich
G J
GJ
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002417:Cattle; D003429:Cross Reactions; D047208:Eosinophil-Derived Neurotoxin; D006801:Humans; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D010179:Pancreas / Q000201:enzymology; D011817:Rabbits; D011863:Radioimmunoassay; D012260:Ribonucleases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D013379:Substrate Specificity
D000906:Antibodies; D007461:Iodoacetates; D009498:Neurotoxins; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases; D019807:Iodoacetic Acid