Differential regulation of the expression of nucleotide pyrophosphatases/phosphodiesterases in rat liver

AbstractWe propose the name nucleotide pyrophosphatases/phosphodiesterases (NPP) for the enzymes that release nucleoside-5′-monophosphates from various pyrophosphate and phosphodiester bonds. Three structurally related mammalian NPPs are known, i.e. NPPα (autotaxin), NPPβ (B10/gp130RB13-6) and NPPγ (PC-1). We report here that these isozymes have a distinct tissue distribution in the rat but that they are all three expressed in hepatocytes. In FAO rat hepatoma cells only the level of NPPγ was stimulated by TGF-β1. In rat liver, the concentration of the transcripts of all three isozymes was found to increase manyfold during the first weeks after birth, but the increased expression of the NPPα mRNA was transient. The level of the NPP transcripts transiently decreased after hepatectomy, but NPPα mRNA was also lost after sham operation, which suggests that it may belong to the negative acute-phase proteins. The loss of the β- and γ-transcripts after hepatectomy was not due to a decreased NPP gene transcription or an increased turnover of the mature transcripts. However, hepatectomy also caused a similar loss of the nuclear pool of the NPPβ and NPPγ mRNAs. We conclude that a deficient processing and/or an increased turnover of the NPP pre-mRNAs underlies the hepatectomy-induced decrease of the β- and γ-transcripts. A similar loss of nuclear NPPγ mRNA was also noted after treatment with cycloheximide, indicating that protein(s) with a high turnover control the stability and/or processing of the immature NPPγ transcript