Loss of selenoprotein W in murine macrophages alters the hierarchy of selenoprotein expression, redox tone, and mitochondrial functions during inflammation
Macrophages play a pivotal role in mediating inflammation and subsequent resolution of inflammation. The availability of selenium as a micronutrient and the subsequent biosynthesis of selenoproteins, containing the 21st amino acid selenocysteine (Sec), are important for the physiological functions o...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722003433 |
| _version_ | 1797954128644669440 |
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| author | Sougat Misra Tai-Jung Lee Aswathy Sebastian John McGuigan Chang Liao Imhoi Koo Andrew D. Patterson Randall M. Rossi Molly A. Hall Istvan Albert K. Sandeep Prabhu |
| author_facet | Sougat Misra Tai-Jung Lee Aswathy Sebastian John McGuigan Chang Liao Imhoi Koo Andrew D. Patterson Randall M. Rossi Molly A. Hall Istvan Albert K. Sandeep Prabhu |
| author_sort | Sougat Misra |
| collection | DOAJ |
| description | Macrophages play a pivotal role in mediating inflammation and subsequent resolution of inflammation. The availability of selenium as a micronutrient and the subsequent biosynthesis of selenoproteins, containing the 21st amino acid selenocysteine (Sec), are important for the physiological functions of macrophages. Selenoproteins regulate the redox tone in macrophages during inflammation, the early onset of which involves oxidative burst of reactive oxygen and nitrogen species. SELENOW is a highly expressed selenoprotein in bone marrow-derived macrophages (BMDMs). Beyond its described general role as a thiol and peroxide reductase and as an interacting partner for 14-3-3 proteins, its cellular functions, particularly in macrophages, remain largely unknown. In this study, we utilized Selenow knock-out (KO) murine bone marrow-derived macrophages (BMDMs) to address the role of SELENOW in inflammation following stimulation with bacterial endotoxin lipopolysaccharide (LPS). RNAseq-based temporal analyses of expression of selenoproteins and the Sec incorporation machinery genes suggested no major differences in the selenium utilization pathway in the Selenow KO BMDMs compared to their wild-type counterparts. However, selective enrichment of oxidative stress-related selenoproteins and increased ROS in Selenow−/− BMDMs indicated anomalies in redox homeostasis associated with hierarchical expression of selenoproteins. Selenow−/− BMDMs also exhibited reduced expression of arginase-1, a key enzyme associated with anti-inflammatory (M2) phenotype necessary to resolve inflammation, along with a significant decrease in efferocytosis of neutrophils that triggers pathways of resolution. Parallel targeted metabolomics analysis also confirmed an impairment in arginine metabolism in Selenow−/− BMDMs. Furthermore, Selenow−/− BMDMs lacked the ability to enhance characteristic glycolytic metabolism during inflammation. Instead, these macrophages atypically relied on oxidative phosphorylation for energy production when glucose was used as an energy source. These findings suggest that SELENOW expression in macrophages may have important implications on cellular redox processes and bioenergetics during inflammation and its resolution. |
| first_indexed | 2024-04-10T23:13:47Z |
| format | Article |
| id | doaj.art-d714f723979e4fb58ae6ded34917a90e |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-10T23:13:47Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-d714f723979e4fb58ae6ded34917a90e2023-01-13T04:16:15ZengElsevierRedox Biology2213-23172023-02-0159102571Loss of selenoprotein W in murine macrophages alters the hierarchy of selenoprotein expression, redox tone, and mitochondrial functions during inflammationSougat Misra0Tai-Jung Lee1Aswathy Sebastian2John McGuigan3Chang Liao4Imhoi Koo5Andrew D. Patterson6Randall M. Rossi7Molly A. Hall8Istvan Albert9K. Sandeep Prabhu10Department of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA, 16802, USADepartment of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA, 16802, USABioinformatics Core, Huck Institute of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USADepartment of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA, 16802, USADepartment of Medicine- Infectious Diseases, University of California, San Francisco, CA, 94143, USAMetabolomics Core Facility, Huck Institute of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USADepartment of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA, 16802, USA; Metabolomics Core Facility, Huck Institute of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USATransgenic Mouse Core Facility, Huck Institute of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USADepartment of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA, 16802, USABioinformatics Core, Huck Institute of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USADepartment of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA, 16802, USA; Corresponding author.Macrophages play a pivotal role in mediating inflammation and subsequent resolution of inflammation. The availability of selenium as a micronutrient and the subsequent biosynthesis of selenoproteins, containing the 21st amino acid selenocysteine (Sec), are important for the physiological functions of macrophages. Selenoproteins regulate the redox tone in macrophages during inflammation, the early onset of which involves oxidative burst of reactive oxygen and nitrogen species. SELENOW is a highly expressed selenoprotein in bone marrow-derived macrophages (BMDMs). Beyond its described general role as a thiol and peroxide reductase and as an interacting partner for 14-3-3 proteins, its cellular functions, particularly in macrophages, remain largely unknown. In this study, we utilized Selenow knock-out (KO) murine bone marrow-derived macrophages (BMDMs) to address the role of SELENOW in inflammation following stimulation with bacterial endotoxin lipopolysaccharide (LPS). RNAseq-based temporal analyses of expression of selenoproteins and the Sec incorporation machinery genes suggested no major differences in the selenium utilization pathway in the Selenow KO BMDMs compared to their wild-type counterparts. However, selective enrichment of oxidative stress-related selenoproteins and increased ROS in Selenow−/− BMDMs indicated anomalies in redox homeostasis associated with hierarchical expression of selenoproteins. Selenow−/− BMDMs also exhibited reduced expression of arginase-1, a key enzyme associated with anti-inflammatory (M2) phenotype necessary to resolve inflammation, along with a significant decrease in efferocytosis of neutrophils that triggers pathways of resolution. Parallel targeted metabolomics analysis also confirmed an impairment in arginine metabolism in Selenow−/− BMDMs. Furthermore, Selenow−/− BMDMs lacked the ability to enhance characteristic glycolytic metabolism during inflammation. Instead, these macrophages atypically relied on oxidative phosphorylation for energy production when glucose was used as an energy source. These findings suggest that SELENOW expression in macrophages may have important implications on cellular redox processes and bioenergetics during inflammation and its resolution.http://www.sciencedirect.com/science/article/pii/S2213231722003433Reactive oxygen speciesMitochondrial respirationMetabolismGlycolysisKrebs cycleEnergy metabolism |
| spellingShingle | Sougat Misra Tai-Jung Lee Aswathy Sebastian John McGuigan Chang Liao Imhoi Koo Andrew D. Patterson Randall M. Rossi Molly A. Hall Istvan Albert K. Sandeep Prabhu Loss of selenoprotein W in murine macrophages alters the hierarchy of selenoprotein expression, redox tone, and mitochondrial functions during inflammation Redox Biology Reactive oxygen species Mitochondrial respiration Metabolism Glycolysis Krebs cycle Energy metabolism |
| title | Loss of selenoprotein W in murine macrophages alters the hierarchy of selenoprotein expression, redox tone, and mitochondrial functions during inflammation |
| title_full | Loss of selenoprotein W in murine macrophages alters the hierarchy of selenoprotein expression, redox tone, and mitochondrial functions during inflammation |
| title_fullStr | Loss of selenoprotein W in murine macrophages alters the hierarchy of selenoprotein expression, redox tone, and mitochondrial functions during inflammation |
| title_full_unstemmed | Loss of selenoprotein W in murine macrophages alters the hierarchy of selenoprotein expression, redox tone, and mitochondrial functions during inflammation |
| title_short | Loss of selenoprotein W in murine macrophages alters the hierarchy of selenoprotein expression, redox tone, and mitochondrial functions during inflammation |
| title_sort | loss of selenoprotein w in murine macrophages alters the hierarchy of selenoprotein expression redox tone and mitochondrial functions during inflammation |
| topic | Reactive oxygen species Mitochondrial respiration Metabolism Glycolysis Krebs cycle Energy metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722003433 |
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