Expression of the liver form of arginase in erythrocytes

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. At is also expressed in various extrahepatic tissues and may play a rote 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. At 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-Al expression is co-dominantly regulated. The M. fascicularis At gene was analyzed to understand At expression in erythrocytes. Erythroid progenitor cells [nucleated red blood cells (nRBCs)] isolated from cord blood were utilized to demonstrate At expression by immunocytochemical staining using anti-Al antibody. Introduction of EGFP reporter vectors into nRBC showed that the proximal 1.2kbp upstream of the At gene is sufficient for At expression. Expression of a second arginase isoform, All, in nRBCs was discovered by cDNA profiling. This contrasts with mature fetal or adult RBCs which contain only the At protein. In addition. an alternatively spliced At (Al') 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. (C) 2002 Elsevier Science (USA). All rights reserved.