Erythroid pyrimidine 5'-nucleotidase: cloning, developmental expression, and regulation by cAMP and in vivo hypoxia.
A characteristic process of terminal erythroid differentiation is the degradation of ribosomal RNA into mononucleotides. The pyrimidine mononucleotides can be dephosphorylated by pyrimidine 5'-nucleotidase (P5N-I). In humans, a lack of this enzyme causes hemolytic anemia with ribosomal structures and trinucleotides retained in the red blood cells (RBCs). Although the protein/nucleotide sequence of P5N-I is known in mammals, the onset and regulation of P5N-I during erythroid maturation is unknown. However, in circulating chicken embryonic RBCs, the enzyme is induced together with carbonic anhydrase (CAII) and 2,3-bisphosphoglycerate (2,3-BPG) by norepinephrine (NE) and adenosine, which are released by the embryo under hypoxic conditions. Here, we present the chicken P5N-I sequence and the gene expression of P5N-I during RBC maturation; the profile of gene expression follows the enzyme activity with a rise between days 13 and 16 of embryonic development. The p5n-I expression is induced (1) in definitive but not primitive RBCs by stimulation of beta-adrenergic/adenosine receptors, and (2) in definitive RBCs by hypoxic incubation of the chicken embryo. Since embryonic RBCs increase their hemoglobin-oxygen affinity by degradation of nucleotides such as uridine triphosphate (UTP) and cytidine triphosphate (CTP), the induction of p5n-I expression can be seen as an adaptive response to hypoxia.
Mass
Markus
M
Physiologisches Institut, Universität Regensburg, 93053 Regensburg, Germany.
Simo
Erika
E
Dragon
Stefanie
S
D019794:2,3-Diphosphoglycerate / Q000378:metabolism; D015720:5'-Nucleotidase / Q000096:biosynthesis* / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D024402:Carbonic Anhydrase II / Q000096:biosynthesis; D002454:Cell Differentiation; D002642:Chick Embryo; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000494:pharmacology*; D004905:Erythrocyte Aging; D004912:Erythrocytes / Q000166:cytology / Q000201:enzymology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D000860:Hypoxia / Q000201:enzymology*; D008969:Molecular Sequence Data; D009638:Norepinephrine / Q000494:pharmacology
D019794:2,3-Diphosphoglycerate; D000242:Cyclic AMP; D015720:5'-Nucleotidase; D024402:Carbonic Anhydrase II; D000241:Adenosine; D009638:Norepinephrine