11 research outputs found
Phosphatidylinositol hydrolysis by human plasma phospholipase D
No full textAbstractA phospholipase D activity able to hydrolyze phosphatidylinositol has previously been described in the cytosol of human neutrophils. The experiments reported here demonstrate that this phosphatidylinositol-hydrolyzing phospholipase D activity is also present in human plasma. This activity was assessed by free inositol release from phosphatidylinositol substrate, by phosphatidate formation and by phosphatidylethanol formation through its capacity of catalyzing a transphosphatidylation reaction. This plasma enzyme activity shows an optimum pH of 8.0 and is inhibited by EGTA
Receptor-mediated activation of arachidonic acid release in mouse peritoneal macrophages is linked to extracellular calcium influx
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Increased incorporation of arachidonic acid into phospholipids in zymosan-stimulated mouse peritoneal macrophages
No full textIncreased Adiposity, Dysregulated Glucose Metabolism and Systemic Inflammation in Galectin-3 KO Mice
No full textPMCID: PMC3579848This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Interplay between hepatic mitochondria-Associated membranes, lipid metabolism and caveolin-1 in mice
No full textThe mitochondria-Associated membrane (MAM) is a specialized subdomain of the endoplasmic reticulum (ER) which acts as an intracellular signaling hub. MAM dysfunction has been related to liver disease. We report a high-Throughput mass spectrometry-based proteomics characterization of MAMs from mouse liver, which portrays them as an extremely complex compartment involved in different metabolic processes, including steroid metabolism. Interestingly, we identified caveolin-1 (CAV1) as an integral component of hepatic MAMs, which determine the relative cholesterol content of these ER subdomains. Finally, a detailed comparative proteomics analysis between MAMs from wild type and CAV1-deficient mice suggests that functional CAV1 contributes to the recruitment and regulation of intracellular steroid and lipoprotein metabolism-related processes accrued at MAMs. The potential impact of these novel aspects of CAV1 biology on global cell homeostasis and disease is discussed
ISG15 Is a Novel Regulator of Lipid Metabolism during Vaccinia Virus Infection.
No full textInterferon-stimulated gene 15 (ISG15) is a 15-kDa ubiquitin-like modifier that binds to target proteins in a process termed ISGylation. ISG15, first described as an antiviral molecule against many viruses, participates in numerous cellular processes, from immune modulation to the regulation of genome stability. Interestingly, the role of ISG15 as a regulator of cell metabolism has recently gained strength. We previously described ISG15 as a regulator of mitochondrial functions in bone marrow-derived macrophages (BMDMs) in the context of Vaccinia virus (VACV) infection. Here, we demonstrate that ISG15 regulates lipid metabolism in BMDMs and that ISG15 is necessary to modulate the impact of VACV infection on lipid metabolism. We show that Isg15-/- BMDMs demonstrate alterations in the levels of several key proteins of lipid metabolism that result in differences in the lipid profile compared with Isg15+/+ (wild-type [WT]) BMDMs. Specifically, Isg15-/- BMDMs present reduced levels of neutral lipids, reflected by decreased lipid droplet number. These alterations are linked to increased levels of lipases and are independent of enhanced fatty acid oxidation (FAO). Moreover, we demonstrate that VACV causes a dysregulation in the proteomes of BMDMs and alterations in the lipid content of these cells, which appear exacerbated in Isg15-/- BMDMs. Such metabolic changes are likely caused by increased expression of the metabolic regulators peroxisome proliferator-activated receptor-γ (PPARγ) and PPARγ coactivator-1α (PGC-1α). In summary, our results highlight that ISG15 controls BMDM lipid metabolism during viral infections, suggesting that ISG15 is an important host factor to restrain VACV impact on cell metabolism. IMPORTANCE The functions of ISG15 are continuously expanding, and growing evidence supports its role as a relevant modulator of cell metabolism. In this work, we highlight how the absence of ISG15 impacts macrophage lipid metabolism in the context of viral infections and how poxviruses modulate metabolism to ensure successful replication. Our results open the door to new advances in the comprehension of macrophage immunometabolism and the interaction between VACV and the host.We thank the expert technical assistance of Sara Sandoval. We are grateful to Miguel
Sánchez-Álvarez who has kindly provided several commercial reagents. We would like
to thank the Spanish National Plan for Scientific and Technical Research and Innovation
(Plan Estatal de Investigación Científica y Técnica y de Innovación), (Ministry of Health
of Spain, State Secretary of R1D and FEDER/FSE).S
Lipin-1-derived diacylglycerol activates intracellular TRPC3 which is critical for inflammatory signaling
No full text© The Author(s) 2021.Exposure to Gram-negative bacterial LPS exacerbates host immune responses and may lead to sepsis, a life-threatening condition. Despite its high mortality and morbidity, no drugs specifically directed to treating sepsis are currently available. Using human cell genetic depletion, pharmacological inhibition, live-cell microscopy and organelle-targeted molecular sensors we present evidence that the channel TRPC3 is activated intracellularly during macrophage exposure to LPS and is essential for Ca2+ release from internal stores. In this manner, TRPC3 participates in cytosolic Ca2+ elevations, activation of the transcription factor NF-κB and cytokine upregulation. We also report that TRPC3 is activated by diacylglycerol generated by the phosphatidic acid phosphatase lipin-1. In accord with this, lipin-1-deficient cells exhibit reduced Ca2+ responses to LPS challenge. Finally, pharmacological inhibition of TRPC3 reduces systemic inflammation induced by LPS in mice. Collectively, our study unveils a central component of LPS-triggered Ca2+ signaling that involves intracellular sensing of lipin-1-derived DAG by TRPC3, and opens new opportunities for the development of strategies to treat LPS-driven inflammation.This work was supported by the Spanish Ministry of Economy, Industry, and Competitiveness (grant SAF2016-80883-R) and the Spanish Ministry of Science and Innovation (grants PID2019-105989RB-I00 and PID2020-118517RB-I00), and the Regional Government of Castile and Leon (grants CSI141P20 and VA172P20, co-financed by the European Union through the European Regional Development Fund). Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas (CIBERDEM) is an initiative of Instituto de Salud Carlos III
ASMase regulates autophagy and lysosomal membrane permeabilization and its inhibition prevents early stage non-alcoholic steatohepatitis
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