Protoporphyrin IX binding and transport by recombinant mouse PBR.
The mitochondrial 18kDa peripheral-type benzodiazepine receptor (PBR), a high affinity cholesterol binding protein, has been shown to interact with protoporphyrin IX (PPIX) and this interaction was assumed to be involved in the regulation of heme biosynthesis and porphyrin-based photodynamic therapy in cancer. In order to test this hypothesis recombinant mouse PBR was expressed in Escherichia coli. The recombinant gene product showed in E. coli protoplasts specific affinity for PPIX binding. PPIX could displace PK 11195 binding. Moreover, induced PBR protein expression in E. coli protoplasts caused an uptake of PPIX that could be completely inhibited by cholesterol and to a lesser extent inhibited by PK 11195 and Ro5-4864. These results suggest that PBR, in addition to its role in cholesterol and coproporphyrinogen III transport, is also directing the mitochondrial PPIX import, a function that can be ascribed to the 18kDa PBR protein alone.
Wendler
Gregor
G
Division of Hormone Research, Departments of Cell Biology, Pharmacology and Neurosciences, Georgetown University School of Medicine, 3900 Reservoir Road, NW, Washington, DC, USA.
Lindemann
Peter
P
Lacapère
Jean-Jacques
JJ
Papadopoulos
Vassilios
V
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins; D002784:Cholesterol / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D034982:Integration Host Factors / Q000235:genetics / Q000378:metabolism; D007546:Isoquinolines / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D021381:Protein Transport / Q000235:genetics / Q000502:physiology*; D011524:Protoporphyrins / Q000235:genetics / Q000378:metabolism*; D018079:Receptors, GABA; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*
C463819:Bzrp protein, mouse; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D034982:Integration Host Factors; D007546:Isoquinolines; D011524:Protoporphyrins; D018079:Receptors, GABA; D011994:Recombinant Proteins; C440502:integration host factor, E coli; D002784:Cholesterol; C028025:protoporphyrin IX; C037850:PK 11195