Stimulation of the activity of prolyl hydroxylase in 3T3 fibroblasts by 1,10-phenanthroline.
In confluent cultures of 3T3 fibroblasts, incubated for 24 h with 1,10-phenanthroline at 10(-5)--10(-9) M, the activity of prolyl hydroxylase was significantly increased. 1,10-Phenanthroline was inhibitory at concentrations greater than 10(-4) M. The stimulatory effect of 1,10-phenanthroline manifests itself after 6 h incubation and increased with time up to 48 h. 2,2'-dipyridyl and 5,6-dimethyl-1,10-phenanthroline were also stimulatory; a nonchelating analog, 1,7-phenanthroline had no effect. Cycloheximide did not modify the 1,10-phenanthroline effect. The stimulatory effect does not seem to depend on the shift of an inactive precursor of prolyl hydroxylase to an active form because 1,10-phenanthroline was shown to be ineffective in logarithmically growing cells. While dialysis of washed and homogenized cells significantly increased prolyl hydroxylase activity in cell extracts, undialyzed 1,10-phenanthroline treated samples exhibited higher prolyl hydroxylase activity than dialyzed controls. These data suggested to us that 1,10-phenanthroline and other chelating agents may be forming complexes with certain metal ions or protein-metal ions which are inhibitory towards prolyl hydroxylase.
D015082:2,2'-Dipyridyl / Q000494:pharmacology; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D010618:Phenanthrolines / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism*; D013997:Time Factors
D010618:Phenanthrolines; D011092:Polyethylene Glycols; D015082:2,2'-Dipyridyl; D004247:DNA; D003513:Cycloheximide; D011393:Procollagen-Proline Dioxygenase