Neutral protease activity and erythropoietin production in the rat after cobalt administration.
The generation of erythropoietin purportedly involves the interaction of an enzyme, of renal origin, and a circulating plasma protein substrate. Cobalt, which has the capacity to stimulate erythropoietin formation, was evaluated for its effects on renal and plasma protease activity; in addition, the nature of the erythrogenic mechanism was investigated. Rats receiving one s.c. injection of cobalt demonstrated significant increases in activity of renal cathepsins A and B. The activity of a plasma protease was also elevated in rats after cobalt treatment. Cathepsins A and B and plasma protease were sensitive to the same enzymatic inhibitory agents, and all three enzymes demonstrated activity patterns similar to that of the renal erythropoietic factor [enzyme(s) presumed responsible for generating erythropoietin] in rats treated with cobalt. These data may help to elucidate the mechanism of erythropoiesis.
D000818:Animals; D002403:Cathepsins / Q000378:metabolism; D003035:Cobalt / Q000494:pharmacology*; D004921:Erythropoietin / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007531:Isoflurophate / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010447:Peptide Hydrolases / Q000097:blood / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
D004921:Erythropoietin; D007531:Isoflurophate; D003035:Cobalt; D002403:Cathepsins; D010447:Peptide Hydrolases