PBRL, a putative peripheral benzodiazepine receptor, in primitive erythropoiesis.
Benzodiazepines are a class of psychoactive drugs widely used for their anxiolytic, anticonvulsant, muscle relaxant and hypnotic properties. Although the benzodiazepine receptor in the central nervous system has been well studied, the role of peripheral type benzodiazepine receptor, PBR, remains elusive. Here, we show that there are two PBR homologous genes in amniotes, PBR and PBRL, based on phylogenetic analysis. In chickens, PBRL is exclusively expressed during early development in differentiating primitive erythrocytes and this expression is tightly correlated with that of hemoglobin genes. PBR is not expressed in hematopoietic system during this period and is weakly expressed in developing central nervous system. Because one of PBRs' known functions is to regulate heme transport between the mitochondria and cytoplasm, we investigated expression profiles of heme biosynthesis genes. Seven of the eight enzymes involved in heme biosynthesis, with the exception of protoporphyrinogen oxidase, are present in chicken genome. Five of them, delta-aminolevulinate synthase, delta-aminolevulinic acid dehydrogenase, porphobilinogen deaminase, coproporphyrinogen decarboxylase and ferrochelatase, show stage-specific increase in gene expression correlated with primitive hematopoiesis, but not with primitive erythrocyte differentiation. PBRL protein is localized to the mitochondria in culture cells, and pharmacological inhibition of PBRL activity results in a decrease in globin protein levels during primitive erythropoiesis. Our data suggest a developmental role of PBRs in erythropoiesis in chickens, possibly via the regulation of heme availability for the assembly of functional hemoglobins.
Nakazawa
Fumie
F
Laboratory for Early Embryogenesis, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.
Alev
Cantas
C
Shin
Masahiro
M
Nakaya
Yukiko
Y
Jakt
Lars M
LM
Sheng
Guojun
G
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics; D002522:Chlorocebus aethiops; D004920:Erythropoiesis / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006418:Heme / Q000096:biosynthesis; D008954:Models, Biological; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D011963:Receptors, GABA-A / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D017385:Sequence Homology
D011963:Receptors, GABA-A; D006418:Heme