Glutathionylation chemistry promotes interleukin‐1 beta‐mediated glycolytic reprogramming and pro‐inflammatory signaling in lung epithelial cells

Autor: Ying-Wai Lam, Vikas Anathy, Cuixia Erickson, Yvonne M. W. Janssen-Heininger, Cheryl van de Wetering, Emiel F.M. Wouters, Reem Aboushousha, Shi B. Chia, Allison M. Manuel, Evan Elko, Maximilian B. MacPherson, Jos van der Velden, David J. Seward, Julie A. Reisz, Angelo D'Alessandro, Niki L. Reynaert, Albert van der Vliet
Přispěvatelé: RS: NUTRIM - R3 - Respiratory & Age-related Health, Pulmonologie
Rok vydání: 2021
Předmět:
0301 basic medicine
LIVER
medicine.medical_treatment
Interleukin-1beta
Biochemistry
Mice
0302 clinical medicine
PYRUVATE-KINASE M2
MITOCHONDRIA
Glycolysis
OXIDATIVE STRESS
Lung
Glyceraldehyde 3-phosphate dehydrogenase
Mice
Knockout
biology
Chemistry
BODY-TEMPERATURE
Cellular Reprogramming
Glutathione
Cell biology
Cytokine
Metabolome
SKELETAL-MUSCLE
Cytokines
Inflammation Mediators
DENDRITIC CELL
Oxidation-Reduction
Reprogramming
Biotechnology
EXPRESSION
Thymic stromal lymphopoietin
SEASONAL-VARIATION
INHIBITION
THERMOGENESIS
HIF-1-ALPHA
PHENOTYPIC FLEXIBILITY
METABOLISM
Pentose phosphate pathway
METABOLOMICS
Protein glutathionylation
Article
MECHANISMS
03 medical and health sciences
Genetics
medicine
Animals
GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE
Molecular Biology
Glutaredoxins
Inflammation
BIRDS
Epithelial Cells
asthma
Mice
Inbred C57BL
Metabolic pathway
030104 developmental biology
biology.protein
glutathionylation
030217 neurology & neurosurgery
Zdroj: FASEB J
Faseb Journal, 35(5):21525. FASEB
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.202002687rr
Popis: Glycolysis is a well-known process by which metabolically active cells, such as tumor or immune cells meet their high metabolic demands. Previously, our laboratory has demonstrated that in airway epithelial cells, the pleiotropic cytokine, interleukin-1 beta (IL1B) induces glycolysis and that this contributes to allergic airway inflammation and remodeling. Activation of glycolysis is known to increase NADPH reducing equivalents generated from the pentose phosphate pathway, linking metabolic reprogramming with redox homeostasis. In addition, numerous glycolytic enzymes are known to be redox regulated. However, whether and how redox chemistry regulates metabolic reprogramming more generally remains unclear. In this study, we employed a multi-omics approach in primary mouse airway basal cells to evaluate the role of protein redox biochemistry, specifically protein glutathionylation, in mediating metabolic reprogramming. Our findings demonstrate that IL1B induces glutathionylation of multiple proteins involved in metabolic regulation, notably in the glycolysis pathway. Cells lacking Glutaredoxin-1 (Glrx), the enzyme responsible for reversing glutathionylation, show modulation of multiple metabolic pathways including an enhanced IL1B-induced glycolytic response. This was accompanied by increased secretion of thymic stromal lymphopoietin (TSLP), a cytokine important in asthma pathogenesis. Targeted inhibition of glycolysis prevented TSLP release, confirming the functional relevance of enhanced glycolysis in cells stimulated with IL1B. Collectively, data herein point to an intriguing link between glutathionylation chemistry and glycolytic reprogramming in epithelial cells and suggest that glutathionylation chemistry may represent a therapeutic target in pulmonary pathologies with perturbations in the glycolysis pathway.
Databáze: OpenAIRE
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