The prolyl 4-hydroxylase inhibitor ethyl-3,4-dihydroxybenzoate generates effective iron deficiency in cultured cells. 2002

Jian Wang, and Joan L Buss, and Guohua Chen, and Prem Ponka, and Kostas Pantopoulos
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote-Ste-Catherine Road, Montreal, Quebec, Canada H3T 1E2.

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.

UI MeSH Term Description Entries
D007501 Iron A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN. Iron-56,Iron 56
D011393 Procollagen-Proline Dioxygenase A mixed-function oxygenase that catalyzes the hydroxylation of a prolyl-glycyl containing peptide, usually in PROTOCOLLAGEN, to a hydroxyprolylglycyl-containing-peptide. The enzyme utilizes molecular OXYGEN with a concomitant oxidative decarboxylation of 2-oxoglutarate to SUCCINATE. The enzyme occurs as a tetramer of two alpha and two beta subunits. The beta subunit of procollagen-proline dioxygenase is identical to the enzyme PROTEIN DISULFIDE-ISOMERASES. Protocollagen Prolyl Hydroxylase,Procollagen Prolyl 4-Hydroxylase,4-Hydroxylase, Procollagen Prolyl,Dioxygenase, Procollagen-Proline,Hydroxylase, Protocollagen Prolyl,Procollagen Proline Dioxygenase,Procollagen Prolyl 4 Hydroxylase,Prolyl 4-Hydroxylase, Procollagen,Prolyl Hydroxylase, Protocollagen
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D000090463 Iron Deficiencies Deficient amounts of iron in the body as a result of blood loss, diets deficient in iron, or an iron uptake or storage disorder. Hypoferritinemia,Iron Deficiency,Latent Iron Deficiency,Sideropenia,Deficiencies, Iron,Deficiencies, Latent Iron,Deficiency, Iron,Deficiency, Latent Iron,Hypoferritinemias,Iron Deficiencies, Latent,Iron Deficiency, Latent,Latent Iron Deficiencies,Sideropenias
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D062385 Hydroxybenzoates Benzoate derivatives substituted by one or more hydroxy groups in any position on the benzene ring. Hydroxybenzoic Acids,Acids, Hydroxybenzoic

Related Publications

Jian Wang, and Joan L Buss, and Guohua Chen, and Prem Ponka, and Kostas Pantopoulos
July 2016, The journal of physiological sciences : JPS,
Jian Wang, and Joan L Buss, and Guohua Chen, and Prem Ponka, and Kostas Pantopoulos
November 2008, Journal of biochemistry,
Jian Wang, and Joan L Buss, and Guohua Chen, and Prem Ponka, and Kostas Pantopoulos
July 1987, The Journal of biological chemistry,
Jian Wang, and Joan L Buss, and Guohua Chen, and Prem Ponka, and Kostas Pantopoulos
August 1989, Nihon Ika Daigaku zasshi,
Jian Wang, and Joan L Buss, and Guohua Chen, and Prem Ponka, and Kostas Pantopoulos
October 1987, The Journal of investigative dermatology,
Jian Wang, and Joan L Buss, and Guohua Chen, and Prem Ponka, and Kostas Pantopoulos
May 2000, The Journal of biological chemistry,
Jian Wang, and Joan L Buss, and Guohua Chen, and Prem Ponka, and Kostas Pantopoulos
April 2010, Critical reviews in biochemistry and molecular biology,
Jian Wang, and Joan L Buss, and Guohua Chen, and Prem Ponka, and Kostas Pantopoulos
June 1980, Biochimica et biophysica acta,
Copied contents to your clipboard!