Itaconic acid is an important metabolite produced by macrophages after stimulation with LPS. The role of itaconate in the inflammatory cascade is unclear. Here we used [C]itaconate and dimethyl [C]itaconate (DMI) to probe itaconate metabolism, and find that [C]DMI is not metabolized to itaconate. [C]Itaconate in the cell culture medium leads to elevated intracellular levels of unlabeled succinate, with no evidence of intracellular uptake. The goal of this study is to encourage the development of effective pro-drug strategies to increase the intracellular levels of itaconate, which will enable more conclusive analysis of its action on macrophages and other cell and tissue types.
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http://dx.doi.org/10.1074/jbc.C117.775270 | DOI Listing |
EMBO Rep
January 2025
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Pro-inflammatory macrophage activation is a hallmark example of how mitochondria serve as signaling organelles. Oxidative phosphorylation sharply decreases upon classical macrophage activation, as mitochondria are thought to shift from ATP production towards accumulating signals that amplify effector function. However, evidence is conflicting regarding whether this collapse in respiration is essential or dispensable.
View Article and Find Full Text PDFBMC Infect Dis
January 2025
Department of Critical Care Medicine, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang Province, China.
Background: The rapid evolution of the COVID-19 pandemic and subsequent global immunization efforts have rendered early metabolomics studies potentially outdated, as they primarily involved non-exposed, non-vaccinated populations. This paper presents a predictive model developed from up-to-date metabolomics data integrated with clinical data to estimate early mortality risk in critically ill COVID-19 patients. Our study addresses the critical gap in current research by utilizing current patient samples, providing fresh insights into the pathophysiology of the disease in a partially immunized global population.
View Article and Find Full Text PDFSignal Transduct Target Ther
December 2024
National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Metabolic reprogramming of host cells plays critical roles during viral infection. Itaconate, a metabolite produced from cis-aconitate in the tricarboxylic acid cycle (TCA) by immune responsive gene 1 (IRG1), is involved in regulating innate immune response and pathogen infection. However, its involvement in viral infection and underlying mechanisms remain incompletely understood.
View Article and Find Full Text PDFMetabolites
December 2024
Fisheries College, Guangdong Ocean University, Zhanjiang 524088, China.
Background: In recent years, titanium dioxide (TiO) nanoparticles (NPs) have been widely used in various industries due to their favorable chemical properties, and their contamination of the environment has attracted much attention, especially to aquatic animals.
Methods: Therefore, we assessed the impact of TiO NPs (5 mg/L) on the marine bivalve, pearl oyster (), especially gill metabolism. Pearl oysters were exposed to seawater containing 5 mg/L TiO NPs for 14 days, followed by 7 days of recovery in untreated seawater.
Biol Direct
December 2024
Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu, 610000, Sichuan, China.
Background: Alveolar macrophages (AMs) is critical to exacerbate acute lung injury (ALI) induced by lipopolysaccharide (LPS) via inhibiting inflammation, which could by shifted by mesenchymal stem cell-derived exosomes (MSC-exos). But the underlying rationale is not fully clarified. Our study aimed to analyze the significance of itaconic acid (ITA) in mediating the protective effects of MSC-exos on LPS-induced ALI.
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