Stimulation of prolyl hydroxylase activity by bleomycin.

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Abstract
The activity of purified prolyl hydroxylase (proline, 2-oxoglutarate dioxygenase, EC 1.14.11.2) was enhanced 3- to 8-fold at a low concentration of ferrous ion (1 .times. 10-5 M) by addition of bleomycin, a glycopeptide antibiotic with antineoplastic activity and a side effect of producing pulmonary fibrosis [in humans]. The maximum stimulation was attained at a concentration of 15 .mu.g/ml bleomycin (about 1 .times. 10-5 M), which was approximately equimolar with the ferrous ion, 1 of the cofactors of this enzyme. Addition of bleomycin to the assay mixture resulted in a change of the optimal concentration of ferrous ion from 2 .times. 10-3 M to 1 .times. 10-5 M. Changing the order of addition of ferrous ion, enzyme and bleomycin in assay medium before incubation at 37.degree. C, the stimulatory activity was varied. Bleomycin A2-Cu2+ (Cu2+-chelated bleomycin), which scarcely complexed with Fe++, had no enhancing effects on the enzymatic activity. The possible reasons why the activity of prolyl hydroxylase was enhanced by addition of bleomycin in the assay mixture [and the relevance of this finding to the mechanism of induction of pulmonary fibrosis by bleomycin] were discussed.

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