Swine workshop cluster 9 (SWC9) antibody identifying a porcine epitope on macrophages and thymocytes was used to precipitate and characterize the molecule from biotinylated macrophages and to obtain peptide sequence by mass spectrometry. The protein was identified as ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1/CD203a). The porcine NPP1/CD203a encoding gene was mapped to chromosome 1 using a radiation hybrid panel, and transcription was investigated by RT-PCR analysis of several tissues. The cDNA was cloned and introduced into COS7 cells resulting in expression of functionally active enzyme and verification of the specificity of an SWC9 reacting monoclonal antibody. The antibody was used for immunohistochemical examination of various porcine tissues. Most prominent expression of NPP1/CD203a was found in lung macrophages and liver sinusoids.
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http://dx.doi.org/10.1016/j.dci.2006.08.012 | DOI Listing |
Amino Acids
December 2024
Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Medicina y Ciencias de la Salud, Universidad de Extremadura, 06006, Badajoz, Spain.
Nucleotide-pyrophosphatases/phosphodiesterases (NPP/PDE) are membrane or secreted Zn-metallohydrolases of nucleoside-5´-monophosphate derivatives. They hydrolyze, for instance, ATP and 4-nitrophenyl-dTMP, and belong to the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family that contains seven members (ENPP1-ENPP7). Earlier we had shown that an NPP/PDE activity solubilized and partially purified from rat liver membranes is inactivated by EDTA in a time-dependent fashion, an effect enhanced by glycine and blocked by the 4-nitrophenyl-dTMP.
View Article and Find Full Text PDFCell Mol Life Sci
September 2024
Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
Background: Dysregulated lipid oxidation occurs in several pathological processes characterized by cell proliferation and migration. Nonetheless, the molecular mechanism of lipid oxidation is not well appreciated in liver fibrosis, which is accompanied by enhanced fibroblast proliferation and migration.
Methods: We investigated the causes and consequences of lipid oxidation in liver fibrosis using cultured cells, animal models, and clinical samples.
Bioorg Med Chem Lett
September 2024
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. Electronic address:
The STING (stimulator of interferon genes) pathway is one of the pathways that regulate innate immunity, and the extracellular hydrolytic enzyme ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) has been identified as its dominant negative regulator. Since activation of the innate immune system is a promising strategy for the treatment of various infectious diseases and cancers, ENPP1 inhibitors have attracted great attention as candidate drugs. We have previously identified small-molecule ENPP1 inhibitors having a [1,2,4]triazolo[1,5-a]pyrimidine scaffold by means of chemical screening using a fluorescence probe, TG-mAMP.
View Article and Find Full Text PDFFree Radic Biol Med
June 2024
Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China. Electronic address:
Background: Dysregulated ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family occurs in metabolic reprogramming pathological processes. Nonetheless, the epigenetic mechanisms by which ENPP family impacts NAFLD, also known as metabolic dysfunction-associated steatotic liver disease (MASLD), is poorly appreciated.
Methods: We investigated the causes and consequences of ENPP1 promoter hypomethylation may boost NAFLD using NAFLD clinical samples, as well as revealed the underlying mechanisms using high-fat diet (HFD) + carbon tetrachloride (CCl) induced mouse model of NAFLD and FFA treatment of cultured hepatocyte.
Eur J Med Chem
March 2024
Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China. Electronic address:
The cancer immunotherapies involved in cGAS-STING pathway have been made great progress in recent years. STING agonists exhibit broad-spectrum anti-tumor effects with strong immune response. As a negative regulator of the cGAS-STING pathway, ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) can hydrolyze extracellular 2', 3'-cGAMP and reduce extracellular 2', 3'-cGAMP concentration.
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