title: The prolyl 4-hydroxylase inhibitor ethyl-3,4-dihydroxybenzoate generates effective iron deficiency in cultured cells.
abstract: Ethyl-3,4-dihydroxybenzoate (EDHB) is commonly utilized as a substrate analog and competitive inhibitor of prolyl 4-hydroxylases. These iron-dependent enzymes have received a lot of attention for their involvement in crucial biochemical pathways such as collagen maturation and oxygen sensing. Since EDHB is also capable of chelating the enzyme-bound iron, we study here its function as a chelator. We show that the affinity of EDHB for ferric iron is significantly lower than that of desferrioxamine. Nevertheless, EDHB is sufficient to promote effective iron deficiency in cells, reflected in the activation of the iron-responsive element/iron regulatory protein regulatory network. Thus, treatment of B6 fibroblasts with EDHB results in slow activation of iron regulatory protein 1 accompanied by an increase in transferrin receptor levels and reduction of the ferritin pool.
authors.affiliation: Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote-Ste-Catherine Road, Montreal, Quebec, Canada H3T 1E2.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Joan L
authors.initials: JL
authors.lastname: Buss
authors.forename: Guohua
authors.initials: G
authors.lastname: Chen
authors.forename: Prem
authors.initials: P
authors.lastname: Ponka
authors.forename: Kostas
authors.initials: K
authors.lastname: Pantopoulos
mesh_terms: D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D062385:Hydroxybenzoates / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism; D000090463:Iron Deficiencies; D051379:Mice; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D062385:Hydroxybenzoates; C018063:ethyl protocatechuate; D007501:Iron; D011393:Procollagen-Proline Dioxygenase