LIVIVO - Search results -

Search results

Result 1 - 10 of total 13

Search options

Article ; Online: Alterations in the molecular control of mitochondrial turnover in COPD lung and airway epithelial cells.

Tulen, Christy B M / van de Wetering, Cheryl / Schiffers, Caspar H J / Weltjens, Ellen / Benedikter, Birke J / Leermakers, Pieter A / Boukhaled, Juliana H / Drittij, Marie-José / Schmeck, Bernd T / Reynaert, Niki L / Opperhuizen, Antoon / van Schooten, Frederik-Jan / Remels, Alexander H V

Scientific reports

2024 Volume 14, Issue 1, Page(s) 4821

Abstract: Abnormal mitochondria have been observed in bronchial- and alveolar epithelial cells of patients with chronic obstructive pulmonary disease (COPD). However, it is unknown if alterations in the molecular pathways regulating mitochondrial turnover ( ... ...

Abstract	Abnormal mitochondria have been observed in bronchial- and alveolar epithelial cells of patients with chronic obstructive pulmonary disease (COPD). However, it is unknown if alterations in the molecular pathways regulating mitochondrial turnover (mitochondrial biogenesis vs mitophagy) are involved. Therefore, in this study, the abundance of key molecules controlling mitochondrial turnover were assessed in peripheral lung tissue from non-COPD patients (n = 6) and COPD patients (n = 11; GOLDII n = 4/11; GOLDIV n = 7/11) and in both undifferentiated and differentiated human primary bronchial epithelial cells (PBEC) from non-COPD patients and COPD patients (n = 4-7 patients/group). We observed significantly decreased transcript levels of key molecules controlling mitochondrial biogenesis (PPARGC1B, PPRC1, PPARD) in peripheral lung tissue from severe COPD patients. Interestingly, mRNA levels of the transcription factor TFAM (mitochondrial biogenesis) and BNIP3L (mitophagy) were increased in these patients. In general, these alterations were not recapitulated in undifferentiated and differentiated PBECs with the exception of decreased PPARGC1B expression in both PBEC models. Although these findings provide valuable insight in these pathways in bronchial epithelial cells and peripheral lung tissue of COPD patients, whether or not these alterations contribute to COPD pathogenesis, underlie changes in mitochondrial function or may represent compensatory mechanisms remains to be established.
MeSH term(s)	Humans ; Lung/pathology ; Pulmonary Disease, Chronic Obstructive/pathology ; Mitochondrial Turnover ; Mitochondria/metabolism ; Epithelial Cells/metabolism ; RNA-Binding Proteins/metabolism
Chemical Substances	PPARGC1B protein, human ; RNA-Binding Proteins
Language	English
Publishing date	2024-02-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-55335-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Phosphomevalonate kinase deficiency expands the genetic spectrum of systemic autoinflammatory diseases.

Berner, Jakob / van de Wetering, Cheryl / Jimenez Heredia, Raul / Rashkova, Christina / Ferdinandusse, Sacha / Koster, Janet / Weiss, Johannes G / Frohne, Alexandra / Giuliani, Sarah / Waterham, Hans R / Castanon, Irinka / Brunner, Jürgen / Boztug, Kaan

The Journal of allergy and clinical immunology

2023 Volume 152, Issue 4, Page(s) 1025–1031.e2

Abstract: Background: In the isoprenoid biosynthesis pathway, mevalonate is phosphorylated in 2 subsequent enzyme steps by MVK and PMVK to generate mevalonate pyrophosphate that is further metabolized to produce sterol and nonsterol isoprenoids. Biallelic ... ...

Abstract	Background: In the isoprenoid biosynthesis pathway, mevalonate is phosphorylated in 2 subsequent enzyme steps by MVK and PMVK to generate mevalonate pyrophosphate that is further metabolized to produce sterol and nonsterol isoprenoids. Biallelic pathogenic variants in MVK result in the autoinflammatory metabolic disorder MVK deficiency. So far, however, no patients with proven PMVK deficiency due to biallelic pathogenic variants in PMVK have been reported. Objectives: This study reports the first patient with functionally confirmed PMVK deficiency, including the clinical, biochemical, and immunological consequences of a homozygous missense variant in PMVK. Methods: The investigators performed whole-exome sequencing and functional studies in cells from a patient who, on clinical and immunological evaluation, was suspected of an autoinflammatory disease. Results: The investigators identified a homozygous PMVK p.Val131Ala (NM_006556.4: c.392T>C) missense variant in the index patient. Pathogenicity was supported by genetic algorithms and modeling analysis and confirmed in patient cells that revealed markedly reduced PMVK enzyme activity due to a virtually complete absence of PMVK protein. Clinically, the patient showed various similarities as well as distinct features compared to patients with MVK deficiency and responded well to therapeutic IL-1 inhibition. Conclusions: This study reported the first patient with proven PMVK deficiency due to a homozygous missense variant in PMVK, leading to an autoinflammatory disease. PMVK deficiency expands the genetic spectrum of systemic autoinflammatory diseases, characterized by recurrent fevers, arthritis, and cytopenia and thus should be included in the differential diagnosis and genetic testing for systemic autoinflammatory diseases.
Language	English
Publishing date	2023-06-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2023.06.013
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Uh III Zs.92: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Downregulation of epithelial DUOX1 in chronic obstructive pulmonary disease.

Schiffers, Caspar / van de Wetering, Cheryl / Bauer, Robert A / Habibovic, Aida / Hristova, Milena / Dustin, Christopher M / Lambrichts, Sara / Vacek, Pamela M / Wouters, Emiel Fm / Reynaert, Niki L / van der Vliet, Albert

JCI insight

2021 Volume 6, Issue 2

Abstract: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by small airway remodeling and alveolar emphysema due to environmental stresses such as cigarette smoking (CS). Oxidative stress is commonly implicated in COPD ... ...

Abstract	Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by small airway remodeling and alveolar emphysema due to environmental stresses such as cigarette smoking (CS). Oxidative stress is commonly implicated in COPD pathology, but recent findings suggest that one oxidant-producing NADPH oxidase homolog, dual oxidase 1 (DUOX1), is downregulated in the airways of patients with COPD. We evaluated lung tissue sections from patients with COPD for small airway epithelial DUOX1 protein expression, in association with measures of lung function and small airway and alveolar remodeling. We also addressed the impact of DUOX1 for lung tissue remodeling in mouse models of COPD. Small airway DUOX1 levels were decreased in advanced COPD and correlated with loss of lung function and markers of emphysema and remodeling. Similarly, DUOX1 downregulation in correlation with extracellular matrix remodeling was observed in a genetic model of COPD, transgenic SPC-TNF-α mice. Finally, development of subepithelial airway fibrosis in mice due to exposure to the CS-component acrolein, or alveolar emphysema induced by administration of elastase, were in both cases exacerbated in Duox1-deficient mice. Collectively, our studies highlight that downregulation of DUOX1 may be a contributing feature of COPD pathogenesis, likely related to impaired DUOX1-mediated innate injury responses involved in epithelial homeostasis.
MeSH term(s)	Aged ; Animals ; Case-Control Studies ; Disease Models, Animal ; Down-Regulation ; Dual Oxidases/genetics ; Dual Oxidases/metabolism ; Extracellular Matrix/pathology ; Extracellular Matrix/physiology ; Female ; Humans ; Lung/pathology ; Lung/physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Middle Aged ; Pulmonary Disease, Chronic Obstructive/enzymology ; Pulmonary Disease, Chronic Obstructive/pathology ; Pulmonary Disease, Chronic Obstructive/physiopathology ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Respiratory Mucosa/pathology ; Respiratory Mucosa/physiopathology
Chemical Substances	RNA, Messenger ; Dual Oxidases (EC 1.11.1.-) ; DUOX1 protein, human (EC 1.6.3.1) ; Duox1 protein, mouse (EC 1.6.3.1)
Language	English
Publishing date	2021-01-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.142189
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Glutathione S-transferases and their implications in the lung diseases asthma and chronic obstructive pulmonary disease: Early life susceptibility?

van de Wetering, Cheryl / Elko, Evan / Berg, Marijn / Schiffers, Caspar H J / Stylianidis, Vasili / van den Berge, Maarten / Nawijn, Martijn C / Wouters, Emiel F M / Janssen-Heininger, Yvonne M W / Reynaert, Niki L

Redox biology

2021 Volume 43, Page(s) 101995

Abstract: Our lungs are exposed daily to airborne pollutants, particulate matter, pathogens as well as lung allergens and irritants. Exposure to these substances can lead to inflammatory responses and may induce endogenous oxidant production, which can cause ... ...

Abstract	Our lungs are exposed daily to airborne pollutants, particulate matter, pathogens as well as lung allergens and irritants. Exposure to these substances can lead to inflammatory responses and may induce endogenous oxidant production, which can cause chronic inflammation, tissue damage and remodeling. Notably, the development of asthma and Chronic Obstructive Pulmonary Disease (COPD) is linked to the aforementioned irritants. Some inhaled foreign chemical compounds are rapidly absorbed and processed by phase I and II enzyme systems critical in the detoxification of xenobiotics including the glutathione-conjugating enzymes Glutathione S-transferases (GSTs). GSTs, and in particular genetic variants of GSTs that alter their activities, have been found to be implicated in the susceptibility to and progression of these lung diseases. Beyond their roles in phase II metabolism, evidence suggests that GSTs are also important mediators of normal lung growth. Therefore, the contribution of GSTs to the development of lung diseases in adults may already start in utero, and continues through infancy, childhood, and adult life. GSTs are also known to scavenge oxidants and affect signaling pathways by protein-protein interaction. Moreover, GSTs regulate reversible oxidative post-translational modifications of proteins, known as protein S-glutathionylation. Therefore, GSTs display an array of functions that impact the pathogenesis of asthma and COPD. In this review we will provide an overview of the specific functions of each class of mammalian cytosolic GSTs. This is followed by a comprehensive analysis of their expression profiles in the lung in healthy subjects, as well as alterations that have been described in (epithelial cells of) asthmatics and COPD patients. Particular emphasis is placed on the emerging evidence of the regulatory properties of GSTs beyond detoxification and their contribution to (un)healthy lungs throughout life. By providing a more thorough understanding, tailored therapeutic strategies can be designed to affect specific functions of particular GSTs.
MeSH term(s)	Animals ; Asthma ; Child ; Glutathione ; Glutathione Transferase ; Humans ; Lung ; Pulmonary Disease, Chronic Obstructive
Chemical Substances	Glutathione Transferase (EC 2.5.1.18) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2021-05-02
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2021.101995
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Dysregulation of Pyruvate Kinase M2 Promotes Inflammation in a Mouse Model of Obese Allergic Asthma.

Manuel, Allison M / van de Wetering, Cheryl / MacPherson, Maximilian / Erickson, Cuixia / Murray, Caliann / Aboushousha, Reem / van der Velden, Jos / Dixon, Anne E / Poynter, Matthew E / Irvin, Charles G / Taatjes, Douglas J / van der Vliet, Albert / Anathy, Vikas / Janssen-Heininger, Yvonne M W

American journal of respiratory cell and molecular biology

2021 Volume 64, Issue 6, Page(s) 709–721

Abstract: Obesity is a risk factor for the development of asthma and represents a difficult-to-treat disease phenotype. Aerobic glycolysis is emerging as a key feature of asthma, and changes in glucose metabolism are linked to leukocyte activation and adaptation ... ...

Abstract	Obesity is a risk factor for the development of asthma and represents a difficult-to-treat disease phenotype. Aerobic glycolysis is emerging as a key feature of asthma, and changes in glucose metabolism are linked to leukocyte activation and adaptation to oxidative stress. Dysregulation of PKM2 (pyruvate kinase M2), the enzyme that catalyzes the last step of glycolysis, contributes to house dust mite (HDM)-induced airway inflammation and remodeling in lean mice. It remains unclear whether glycolytic reprogramming and dysregulation of PKM2 also contribute to obese asthma. The goal of the present study was to elucidate the functional role of PKM2 in a murine model of obese allergic asthma. We evaluated the small molecule activator of PKM2, TEPP46, and assessed the role of PKM2 using conditional ablation of the
MeSH term(s)	Animals ; Asthma/complications ; Asthma/enzymology ; Asthma/parasitology ; Asthma/pathology ; Bronchial Hyperreactivity/complications ; Diet, High-Fat ; Disease Models, Animal ; Enzyme Activation/drug effects ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Glutathione/metabolism ; Glycolysis ; Homeostasis/drug effects ; Hypersensitivity/complications ; Hypersensitivity/enzymology ; Hypersensitivity/parasitology ; Hypersensitivity/pathology ; Inflammation/enzymology ; Inflammation/pathology ; Inflammation Mediators/metabolism ; Lung/enzymology ; Lung/pathology ; Mice, Inbred C57BL ; Mice, Obese ; Models, Biological ; Pyridazines/administration & dosage ; Pyridazines/pharmacology ; Pyroglyphidae ; Pyrroles/administration & dosage ; Pyrroles/pharmacology ; Pyruvate Kinase/metabolism ; Mice
Chemical Substances	Inflammation Mediators ; ML-265 ; Pyridazines ; Pyrroles ; Pyruvate Kinase (EC 2.7.1.40) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2021-03-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1025960-0
ISSN	1535-4989 ; 1044-1549
ISSN (online)	1535-4989
ISSN	1044-1549
DOI	10.1165/rcmb.2020-0512OC
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2851: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Biallelic NFATC1 mutations cause an inborn error of immunity with impaired CD8+ T-cell function and perturbed glycolysis.

Kostel Bal, Sevgi / Giuliani, Sarah / Block, Jana / Repiscak, Peter / Hafemeister, Christoph / Shahin, Tala / Kasap, Nurhan / Ransmayr, Bernhard / Miao, Yirun / van de Wetering, Cheryl / Frohne, Alexandra / Jimenez Heredia, Raul / Schuster, Michael / Zoghi, Samaneh / Hertlein, Vanessa / Thian, Marini / Bykov, Aleksandr / Babayeva, Royala / Bilgic Eltan, Sevgi /

Karakoc-Aydiner, Elif / Shaw, Lisa E / Chowdhury, Iftekhar / Varjosalo, Markku / Argüello, Rafael J / Farlik, Matthias / Ozen, Ahmet / Serfling, Edgar / Dupré, Loïc / Bock, Christoph / Halbritter, Florian / Hannich, J Thomas / Castanon, Irinka / Kraakman, Michael J / Baris, Safa / Boztug, Kaan

Blood

2023 Volume 142, Issue 9, Page(s) 827–845

Abstract: The nuclear factor of activated T cells (NFAT) family of transcription factors plays central roles in adaptive immunity in murine models; however, their contribution to human immune homeostasis remains poorly defined. In a multigenerational pedigree, we ... ...

Abstract	The nuclear factor of activated T cells (NFAT) family of transcription factors plays central roles in adaptive immunity in murine models; however, their contribution to human immune homeostasis remains poorly defined. In a multigenerational pedigree, we identified 3 patients who carry germ line biallelic missense variants in NFATC1, presenting with recurrent infections, hypogammaglobulinemia, and decreased antibody responses. The compound heterozygous NFATC1 variants identified in these patients caused decreased stability and reduced the binding of DNA and interacting proteins. We observed defects in early activation and proliferation of T and B cells from these patients, amenable to rescue upon genetic reconstitution. Stimulation induced early T-cell activation and proliferation responses were delayed but not lost, reaching that of healthy controls at day 7, indicative of an adaptive capacity of the cells. Assessment of the metabolic capacity of patient T cells revealed that NFATc1 dysfunction rendered T cells unable to engage in glycolysis after stimulation, although oxidative metabolic processes were intact. We hypothesized that NFATc1-mutant T cells could compensate for the energy deficit due to defective glycolysis by using enhanced lipid metabolism as an adaptation, leading to a delayed, but not lost, activation responses. Indeed, we observed increased 13C-labeled palmitate incorporation into citrate, indicating higher fatty acid oxidation, and we demonstrated that metformin and rosiglitazone improved patient T-cell effector functions. Collectively, enabled by our molecular dissection of the consequences of loss-of-function NFATC1 mutations and extending the role of NFATc1 in human immunity beyond receptor signaling, we provide evidence of metabolic plasticity in the context of impaired glycolysis observed in patient T cells, alleviating delayed effector responses.
MeSH term(s)	Humans ; Mice ; Animals ; T-Lymphocytes/metabolism ; NFATC Transcription Factors/metabolism ; CD8-Positive T-Lymphocytes ; Glycolysis/genetics ; Mutation
Chemical Substances	NFATC Transcription Factors ; NFATC1 protein, human
Language	English
Publishing date	2023-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022018303
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 364: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Glutathionylation chemistry promotes interleukin-1 beta-mediated glycolytic reprogramming and pro-inflammatory signaling in lung epithelial cells.

Aboushousha, Reem / Elko, Evan / Chia, Shi B / Manuel, Allison M / van de Wetering, Cheryl / van der Velden, Jos / MacPherson, Maximilian / Erickson, Cuixia / Reisz, Julie A / D'Alessandro, Angelo / Wouters, Emiel F M / Reynaert, Niki L / Lam, Ying-Wai / Anathy, Vikas / van der Vliet, Albert / Seward, David J / Janssen-Heininger, Yvonne M W

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2021 Volume 35, Issue 5, Page(s) e21525

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Animals ; Cellular Reprogramming ; Cytokines/metabolism ; Epithelial Cells/cytology ; Epithelial Cells/drug effects ; Epithelial Cells/immunology ; Epithelial Cells/metabolism ; Glutaredoxins/physiology ; Glutathione/metabolism ; Glycolysis ; Inflammation/immunology ; Inflammation/metabolism ; Inflammation/pathology ; Inflammation Mediators/metabolism ; Interleukin-1beta/pharmacology ; Lung/cytology ; Lung/drug effects ; Lung/immunology ; Lung/metabolism ; Metabolome ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oxidation-Reduction
Chemical Substances	Cytokines ; Glrx protein, mouse ; Glutaredoxins ; Inflammation Mediators ; Interleukin-1beta ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2021-04-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202002687RR
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2266: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 296: Show issues

Order via subito

Details ▾

Article ; Online: Dysregulation of the glutaredoxin/

Chia, Shi B / Elko, Evan A / Aboushousha, Reem / Manuel, Allison M / van de Wetering, Cheryl / Druso, Joseph E / van der Velden, Jos / Seward, David J / Anathy, Vikas / Irvin, Charles G / Lam, Ying-Wai / van der Vliet, Albert / Janssen-Heininger, Yvonne M W

American journal of physiology. Cell physiology

2019 Volume 318, Issue 2, Page(s) C304–C327

Abstract: Glutathione is a major redox buffer, reaching millimolar concentrations within cells and high micromolar concentrations in airways. While glutathione has been traditionally known as an antioxidant defense mechanism that protects the lung tissue from ... ...

Abstract	Glutathione is a major redox buffer, reaching millimolar concentrations within cells and high micromolar concentrations in airways. While glutathione has been traditionally known as an antioxidant defense mechanism that protects the lung tissue from oxidative stress, glutathione more recently has become recognized for its ability to become covalently conjugated to reactive cysteines within proteins, a modification known as
MeSH term(s)	Amino Acid Sequence ; Animals ; Antioxidants/metabolism ; Cysteine/metabolism ; Disulfides/metabolism ; Glutaredoxins/metabolism ; Glutathione/metabolism ; Humans ; Lung/metabolism ; Lung Diseases/metabolism ; Mice ; Mice, Inbred BALB C ; Oxidation-Reduction ; Oxidative Stress/physiology
Chemical Substances	Antioxidants ; Disulfides ; GLRX protein, human ; Glutaredoxins ; Glutathione (GAN16C9B8O) ; Cysteine (K848JZ4886)
Language	English
Publishing date	2019-11-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00410.2019
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.89: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Peroxiredoxins and Beyond; Redox Systems Regulating Lung Physiology and Disease.

Elko, Evan A / Cunniff, Brian / Seward, David J / Chia, Shi Biao / Aboushousha, Reem / van de Wetering, Cheryl / van der Velden, Jos / Manuel, Allison / Shukla, Arti / Heintz, Nicholas H / Anathy, Vikas / van der Vliet, Albert / Janssen-Heininger, Yvonne M W

Antioxidants & redox signaling

2019 Volume 31, Issue 14, Page(s) 1070–1091

Abstract: Significance: ...

Abstract	Significance:
MeSH term(s)	Animals ; Humans ; Lung/metabolism ; Lung Diseases/metabolism ; Oxidation-Reduction ; Peroxiredoxins/metabolism
Chemical Substances	Peroxiredoxins (EC 1.11.1.15)
Language	English
Publishing date	2019-04-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2019.7752
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5488: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Pyruvate Kinase M2 Promotes Expression of Proinflammatory Mediators in House Dust Mite-Induced Allergic Airways Disease.

van de Wetering, Cheryl / Aboushousha, Reem / Manuel, Allison M / Chia, Shi B / Erickson, Cuixia / MacPherson, Maximilian B / van der Velden, Jos L / Anathy, Vikas / Dixon, Anne E / Irvin, Charles G / Poynter, Matthew E / van der Vliet, Albert / Wouters, Emiel F M / Reynaert, Niki L / Janssen-Heininger, Yvonne M W

Journal of immunology (Baltimore, Md. : 1950)

2020 Volume 204, Issue 4, Page(s) 763–774

Abstract: Asthma is a chronic disorder characterized by inflammation, mucus metaplasia, airway remodeling, and hyperresponsiveness. We recently showed that IL-1-induced glycolytic reprogramming contributes to allergic airway disease using a murine house dust mite ... ...

Abstract	Asthma is a chronic disorder characterized by inflammation, mucus metaplasia, airway remodeling, and hyperresponsiveness. We recently showed that IL-1-induced glycolytic reprogramming contributes to allergic airway disease using a murine house dust mite model. Moreover, levels of pyruvate kinase M2 (PKM2) were increased in this model as well as in nasal epithelial cells from asthmatics as compared with healthy controls. Although the tetramer form of PKM2 converts phosphoenolpyruvate to pyruvate, the dimeric form of PKM2 has alternative, nonglycolysis functions as a transcriptional coactivator to enhance the transcription of several proinflammatory cytokines. In the current study, we examined the impact of PKM2 on the pathogenesis of house dust mite-induced allergic airways disease in C57BL/6NJ mice. We report, in this study, that activation of PKM2, using the small molecule activator, TEPP46, augmented PKM activity in lung tissues and attenuated airway eosinophils, mucus metaplasia, and subepithelial collagen. TEPP46 attenuated IL-1β-mediated airway inflammation and expression of proinflammatory mediators. Exposure to TEPP46 strongly decreased the IL-1β-mediated increases in thymic stromal lymphopoietin (TSLP) and GM-CSF in primary tracheal epithelial cells isolated from C57BL/6NJ mice. We also demonstrate that IL-1β-mediated increases in nuclear phospho-STAT3 were decreased by TEPP46. Finally, STAT3 inhibition attenuated the IL-1β-induced release of TSLP and GM-CSF, suggesting that the ability of PKM2 to phosphorylate STAT3 contributes to its proinflammatory function. Collectively, these results demonstrate that the glycolysis-inactive form of PKM2 plays a crucial role in the pathogenesis of allergic airways disease by increasing IL-1β-induced proinflammatory signaling, in part, through phosphorylation of STAT3.
MeSH term(s)	Airway Remodeling/physiology ; Animals ; Asthma/immunology ; Asthma/metabolism ; Female ; Hypersensitivity/immunology ; Hypersensitivity/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Pneumonia/immunology ; Pneumonia/metabolism ; Pyroglyphidae/immunology ; Pyruvate Kinase/immunology ; Pyruvate Kinase/metabolism ; Signal Transduction/immunology
Chemical Substances	Pkm protein, mouse (EC 2.7.1.40) ; Pyruvate Kinase (EC 2.7.1.40)
Language	English
Publishing date	2020-01-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1901086
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 28: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

Your last searches

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito