Linked Life Data

18299324

Source:http://linkedlifedata.com/resource/pubmed/id/18299324

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2008-4-28
pubmed:abstractText
The heme protein indoleamine 2,3-dioxygenase (IDO) initiates oxidative metabolism of tryptophan along the kynurenine pathway, and this requires reductive activation of Fe(3+)-IDO. The current dogma is that superoxide anion radical (O(2)(*-)) is responsible for this activation, based largely on previous work employing purified rabbit IDO and rabbit enterocytes. We have re-investigated this role of O(2)(*-) using purified recombinant human IDO (rhIDO), rabbit enterocytes that constitutively express IDO, human endothelial cells, and monocyte-derived macrophages treated with interferon-gamma to induce IDO expression, and two cell lines transfected with the human IDO gene. Both potassium superoxide and O(2)(*-) generated by xanthine oxidase modestly activated rhIDO, in reactions that were prevented completely by superoxide dismutase (SOD). In contrast, SOD mimetics had no effect on IDO activity in enterocytes and interferon-gamma-treated human cells, despite significantly decreasing cellular O(2)(*-) Similarly, cellular IDO activity was unaffected by increasing SOD activity via co-expression of Cu,Zn-SOD or by increasing cellular O(2)(*-) via treatment of cells with menadione. Other reductants, such as tetrahydrobiopterin, ascorbate, and cytochrome P450 reductase, were ineffective in activating cellular IDO. However, recombinant human cytochrome b(5) plus cytochrome P450 reductase and NADPH reduced Fe(3+)-IDO to Fe(2+)-IDO and activated rhIDO in a reconstituted system, a reaction inhibited marginally by SOD. Additionally, short interfering RNA-mediated knockdown of microsomal cytochrome b(5) significantly decreased IDO activity in IDO-transfected cells. Together, our data show that cytochrome b(5) rather than O(2)(*-) plays a major role in the activation of IDO in human cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12014-25
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18299324-Animals, pubmed-meshheading:18299324-CHO Cells, pubmed-meshheading:18299324-Cattle, pubmed-meshheading:18299324-Cricetinae, pubmed-meshheading:18299324-Cricetulus, pubmed-meshheading:18299324-Cytochromes b5, pubmed-meshheading:18299324-Endothelial Cells, pubmed-meshheading:18299324-Enterocytes, pubmed-meshheading:18299324-Enzyme Activation, pubmed-meshheading:18299324-Flavin Mononucleotide, pubmed-meshheading:18299324-Humans, pubmed-meshheading:18299324-Indoleamine-Pyrrole 2,3,-Dioxygenase, pubmed-meshheading:18299324-Interferon-gamma, pubmed-meshheading:18299324-Oxidation-Reduction, pubmed-meshheading:18299324-Rabbits, pubmed-meshheading:18299324-Recombinant Proteins, pubmed-meshheading:18299324-Reducing Agents, pubmed-meshheading:18299324-Superoxide Dismutase, pubmed-meshheading:18299324-Superoxides, pubmed-meshheading:18299324-Transfection
pubmed:year
2008
pubmed:articleTitle
Cytochrome b5, not superoxide anion radical, is a major reductant of indoleamine 2,3-dioxygenase in human cells.
pubmed:affiliation
Centre for Vascular Research and Molecular Immunopathology Unit, Bosch Institute and Discipline of Pathology, School of Medical Sciences, University of Sydney, Sydney, New South Wales 2006, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't