ArticleThe Journal of biological chemistry2014
Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a novel nucleotide phosphodiesterase regulated by cholesterol in human macrophages.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
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- Free amino acids accelerate the time-dependent inactivation of rat liver nucleotide pyrophosphatase/phosphodiesterase Enpp3 elicited by EDTA.Amino acids · 2024Article
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- Differences in the Genomic Profiles of Immunoparalyzed and Nonimmunoparalyzed Children With Sepsis: A Pilot Study.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2022Observational
- Rare Variants in the DNA Repair Pathway and the Risk of Colorectal Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2021Article
- Expanding the Genotypic Spectrum of Congenital Sensory and Autonomic Neuropathies Using Whole-Exome Sequencing.Neurology. Genetics · 2021Article
- Hypothalamic transcriptome of tame and aggressive silver foxes (Vulpes vulpes) identifies gene expression differences shared across brain regions.Genes, brain, and behavior · 2020Article
- Regulation of the amount of ceramide-1-phosphate synthesized in differentiated human podocytes.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Article
- Transcriptomics analysis of host liver and meta-transcriptome analysis of rumen epimural microbial community in young calves treated with artificial dosing of rumen content from adult donor cow.Scientific reports · 2019Article
- Deregulation of obesity-relevant genes is associated with progression in BMI and the amount of adipose tissue in pigs.Molecular genetics and genomics : MGG · 2018Article
- Identification of diverse target RNAs that are functionally regulated by human Pumilio proteins.Nucleic acids research · 2018Article
- Crystal Structure of the Acid Sphingomyelinase-like Phosphodiesterase SMPDL3B Provides Insights into Determinants of Substrate Specificity.The Journal of biological chemistry · 2016Article
- Crystal structure of mammalian acid sphingomyelinase.Nature communications · 2016Article
- Structural Basis for Nucleotide Hydrolysis by the Acid Sphingomyelinase-like Phosphodiesterase SMPDL3A.The Journal of biological chemistry · 2016Article
- Joint Profiling of miRNAs and mRNAs Reveals miRNA Mediated Gene Regulation in the Göttingen Minipig Obesity Model.PloS one · 2016Article
- Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity.Journal of diabetes research · 2016Article
- The Lipid-Modifying Enzyme SMPDL3B Negatively Regulates Innate Immunity.Cell reports · 2015Article
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholesterol-loaded foam cell macrophages are prominent in atherosclerotic lesions and play complex roles in both inflammatory signaling and lipid metabolism, which are underpinned by large scale reprogramming of gene expression. We performed a microarray study of primary human macrophages that showed that transcription of the sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) gene is up-regulated after cholesterol loading. SMPDL3A protein expression in and secretion from primary macrophages are stimulated by cholesterol loading, liver X receptor ligands, and cyclic AMP, and N-glycosylated SMPDL3A protein is detectable in circulating blood. We demonstrate for the first time that SMPDL3A is a functional phosphodiesterase with an acidic pH optimum. We provide evidence that SMPDL3A is not an acid sphingomyelinase but unexpectedly is active against nucleotide diphosphate and triphosphate substrates at acidic and neutral pH. SMPDL3A is a major source of nucleotide phosphodiesterase activity secreted by liver X receptor-stimulated human macrophages. Extracellular nucleotides such as ATP may activate pro-inflammatory responses in immune cells. Increased expression and secretion of SMPDL3A by cholesterol-loaded macrophage foam cells in lesions may decrease local concentrations of pro-inflammatory nucleotides and potentially represent a novel anti-inflammatory axis linking lipid metabolism with purinergic signaling in atherosclerosis.
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