title: Expression of the liver form of arginase in erythrocytes.
abstract: Arginase I (AI) has a critical function in mammalian liver as the final enzyme in the urea cycle responsible for the disposal of ammonia from protein catabolism. AI is also expressed in various extrahepatic tissues and may play a role in regulating arginine levels and in providing ornithine for biosynthetic reactions that generate various critical intermediary metabolites such as glutamate, glutamine, GABA, agmatine, polyamines, creatine, proline, and nitric oxide. AI is expressed in red blood cells (RBCs) only in humans and certain higher primates. Macaca fascicularis has been identified as an evolutionary transition species in which RBC-AI expression is co-dominantly regulated. The M. fascicularis AI gene was analyzed to understand AI expression in erythrocytes. Erythroid progenitor cells [nucleated red blood cells (nRBCs)] isolated from cord blood were utilized to demonstrate AI expression by immunocytochemical staining using anti-AI antibody. Introduction of EGFP reporter vectors into nRBC showed that the proximal 1.2 kbp upstream of the AI gene is sufficient for AI expression. Expression of a second arginase isoform, AII, in nRBCs was discovered by cDNA profiling. This contrasts with mature fetal or adult RBCs which contain only the AI protein. In addition, an alternatively spliced AI (AI(')) variant was observed from erythroid mRNA analysis with an alternative splice acceptor site located within intron 2, causing the insertion of eight additional amino acids yet retaining significant enzymatic activity.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California at Los Angeles School of Medicine, 10833 Le Conte Avenue, 90095-1732, USA.
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Kim
authors.forename: Ramaswamy K
authors.initials: RK
authors.lastname: Iyer
authors.forename: Kan V
authors.initials: KV
authors.lastname: Lu
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Karimi
authors.forename: Rita M
authors.initials: RM
authors.lastname: Kern
authors.forename: Denice K
authors.initials: DK
authors.lastname: Tai
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Cederbaum
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Grody
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001119:Arginase / Q000097:blood / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D004912:Erythrocytes / Q000201:enzymology*; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008252:Macaca fascicularis / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D001119:Arginase