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Article ; Online: Species-specific NLRP3 regulation and its role in CNS autoinflammatory diseases.

Koller, Beverly H / Nguyen, MyTrang / Snouwaert, John N / Gabel, Christopher A / Ting, Jenny P-Y

2024 Volume 43, Issue 3, Page(s) 113852

Abstract: The NLRP3 inflammasome is essential for caspase-1 activation and the release of interleukin (IL)-1β, IL-18, and gasdermin-D in myeloid cells. However, research on species-specific NLRP3's physiological impact is limited. We engineer mice with the human ... ...

Abstract	The NLRP3 inflammasome is essential for caspase-1 activation and the release of interleukin (IL)-1β, IL-18, and gasdermin-D in myeloid cells. However, research on species-specific NLRP3's physiological impact is limited. We engineer mice with the human NLRP3 gene, driven by either the human or mouse promoter, via syntenic replacement at the mouse Nlrp3 locus. Both promoters facilitate hNLRP3 expression in myeloid cells, but the mouse promoter responds more robustly to LPS. Investigating the disease impact of differential NLRP3 regulation, we introduce the D305N gain-of-function mutation into both humanized lines. Chronic inflammation is evident with both promoters; however, CNS outcomes vary significantly. Despite poor response to LPS, the human promoter results in D305N-associated aseptic meningitis, mirroring human pathology. The mouse promoter, although leading to increased CNS expression post-LPS, does not induce meningitis in D305N mutants. Therefore, human-like NLRP3 expression may be crucial for accurate modeling of its role in disease pathogenesis.
MeSH term(s)	Humans ; Animals ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Lipopolysaccharides/pharmacology ; Inflammasomes/metabolism ; Inflammation ; Syndrome ; Hereditary Autoinflammatory Diseases ; Interleukin-1beta/metabolism ; Caspase 1/metabolism
Chemical Substances	NLR Family, Pyrin Domain-Containing 3 Protein ; Lipopolysaccharides ; Inflammasomes ; Interleukin-1beta ; Caspase 1 (EC 3.4.22.36)
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2024.113852
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Article ; Online: Metabolism of Inorganic Arsenic in Mice Lacking Genes Encoding GST-P, GST-M, and GST-T.

Douillet, Christelle / Koller, Beverly H / Stýblo, Miroslav

Chemical research in toxicology

2020 Volume 33, Issue 8, Page(s) 2043–2046

Abstract: To investigate the role of glutathione transferases (GSTs) in the metabolism of inorganic arsenic (iAs), we compared the disposition of iAs and its metabolites in wild-type mice and mice lacking genes encoding GST-P, -M and -T after exposure to 100 ppb ... ...

Abstract	To investigate the role of glutathione transferases (GSTs) in the metabolism of inorganic arsenic (iAs), we compared the disposition of iAs and its metabolites in wild-type mice and mice lacking genes encoding GST-P, -M and -T after exposure to 100 ppb iAs in drinking water. We found no differences between the two genotypes in the concentrations of total arsenic or arsenic species in urine, liver, and kidneys. No genotype-dependent differences were found in proportions of arsenicals in the tissues, and only small differences were observed in the urine. Thus, under these conditions, GST-P, -M and -T did not play a significant role in iAs metabolism in mice.
MeSH term(s)	Animals ; Arsenic/administration & dosage ; Arsenic/analysis ; Arsenic/metabolism ; Drinking Water/administration & dosage ; Drinking Water/analysis ; Drinking Water/metabolism ; Environmental Exposure/analysis ; Glutathione Transferase/genetics ; Glutathione Transferase/metabolism ; Mice
Chemical Substances	Drinking Water ; Glutathione Transferase (EC 2.5.1.18) ; Arsenic (N712M78A8G)
Language	English
Publishing date	2020-07-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639353-6
ISSN	1520-5010 ; 0893-228X
ISSN (online)	1520-5010
ISSN	0893-228X
DOI	10.1021/acs.chemrestox.0c00273
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Article ; Online: Molecular and Metabolic Analysis of Arsenic-Exposed Humanized AS3MT Mice.

Todero, Jenna / Douillet, Christelle / Shumway, Alexandria J / Koller, Beverly H / Kanke, Matt / Phuong, Daryl J / Stýblo, Miroslav / Sethupathy, Praveen

Environmental health perspectives

2023 Volume 131, Issue 12, Page(s) 127021

Abstract: Background: Chronic exposure to inorganic arsenic (iAs) has been associated with type 2 diabetes (T2D). However, potential sex divergence and the underlying mechanisms remain understudied. iAs is not metabolized uniformly across species, which is a ... ...

Abstract	Background: Chronic exposure to inorganic arsenic (iAs) has been associated with type 2 diabetes (T2D). However, potential sex divergence and the underlying mechanisms remain understudied. iAs is not metabolized uniformly across species, which is a limitation of typical exposure studies in rodent models. The development of a new "humanized" mouse model overcomes this limitation. In this study, we leveraged this model to study sex differences in the context of iAs exposure. Objectives: The aim of this study was to determine if males and females exhibit different liver and adipose molecular profiles and metabolic phenotypes in the context of iAs exposure. Methods: Our study was performed on wild-type (WT) 129S6/SvEvTac and humanized arsenic Results: We detected sex divergence in liver and adipose markers of diabetes (e.g., miR-34a, insulin signaling pathways, fasting blood glucose, fasting plasma insulin, and HOMA-IR) only in humanized (not WT) mice. In humanized female mice, numerous genes that promote insulin sensitivity and glucose tolerance in both the liver and adipose are elevated compared to humanized male mice. We also identified Klf11 as a putative master regulator of the sex divergence in gene expression in humanized mice. Discussion: Our study underscored the importance of future studies leveraging the humanized mouse model to study iAs-associated metabolic disease. The findings suggested that humanized males are at increased risk for metabolic dysfunction relative to humanized females in the context of iAs exposure. Future investigations should focus on the detailed mechanisms that underlie the sex divergence. https://doi.org/10.1289/EHP12785.
MeSH term(s)	Female ; Male ; Mice ; Humans ; Animals ; Arsenic/analysis ; Blood Glucose/analysis ; Diabetes Mellitus, Type 2/chemically induced ; Arsenicals ; Insulin Resistance ; Insulin ; Obesity ; Methyltransferases/genetics
Chemical Substances	Arsenic (N712M78A8G) ; Blood Glucose ; Arsenicals ; Insulin ; AS3MT protein, human (EC 2.1.1.137) ; Methyltransferases (EC 2.1.1.-) ; AS3MT protein, mouse (EC 2.1.1.137)
Language	English
Publishing date	2023-12-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	195189-0
ISSN	1552-9924 ; 0091-6765 ; 1078-0475
ISSN (online)	1552-9924
ISSN	0091-6765 ; 1078-0475
DOI	10.1289/EHP12785
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Article ; Online: Target Cell Activation of a Structurally Novel NOD-Like Receptor Pyrin Domain-Containing Protein 3 Inhibitor NT-0796 Enhances Potency.

Smolak, Pamela / Nguyen, MyTrang / Diamond, Christine / Wescott, Heather / Doedens, John R / Schooley, Kenneth / Snouwaert, John N / Bock, Mark G / Harrison, David / Watt, Alan P / Koller, Beverly H / Gabel, Christopher A

The Journal of pharmacology and experimental therapeutics

2024 Volume 388, Issue 3, Page(s) 798–812

Abstract: The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is a central regulator of innate immunity, essential for processing and release of interleukin- ... ...

Abstract	The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is a central regulator of innate immunity, essential for processing and release of interleukin-1
MeSH term(s)	Humans ; Animals ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; NLR Proteins ; Pyrin Domain ; Inflammasomes/metabolism ; Caspase 1/metabolism ; Esters ; Carboxylic Ester Hydrolases/metabolism ; Interleukin-1beta/metabolism
Chemical Substances	NLR Family, Pyrin Domain-Containing 3 Protein ; NLR Proteins ; Inflammasomes ; Caspase 1 (EC 3.4.22.36) ; Esters ; Carboxylic Ester Hydrolases (EC 3.1.1.-) ; Interleukin-1beta
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
DOI	10.1124/jpet.123.001941
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Article ; Online: Cell-Specific Actions of the Prostaglandin E-Prostanoid Receptor 4 Attenuating Hypertension: A Dominant Role for Kidney Epithelial Cells Compared With Macrophages.

Yang, Ting / Song, Chengcheng / Ralph, Donna L / Andrews, Portia / Sparks, Matthew A / Koller, Beverly H / McDonough, Alicia A / Coffman, Thomas M

Journal of the American Heart Association

2022 Volume 11, Issue 19, Page(s) e026581

Abstract: Background A beneficial role for prostanoids in hypertension is suggested by clinical studies showing nonsteroidal anti-inflammatory drugs, which block the production of all prostanoids, cause sodium retention and exacerbate hypertension. Among ... ...

Abstract	Background A beneficial role for prostanoids in hypertension is suggested by clinical studies showing nonsteroidal anti-inflammatory drugs, which block the production of all prostanoids, cause sodium retention and exacerbate hypertension. Among prostanoids, prostaglandin E2 and its E-prostanoid receptor 4 receptor (EP4R) have been implicated in blood pressure control. Our previous study found that conditional deletion of EP4R from all tissues in adult mice exacerbates angiotensin II-dependent hypertension, suggesting a powerful effect of EP4R to resist blood pressure elevation. We also found that elimination of EP4R from vascular smooth muscle cells did not affect the severity of hypertension, suggesting nonvascular targets of prostaglandin E mediate this antihypertensive effect. Methods and Results Here we generated mice with cell-specific deletion of EP4R from macrophage-specific EP4 receptor knockouts or kidney epithelial cells (KEKO) to assess the contributions of EP4R in these cells to hypertension pathogenesis. Macrophage-specific EP4 receptor knockouts showed similar blood pressure responses to alterations in dietary sodium or chronic angiotensin II infusion as Controls. By contrast, angiotensin II-dependent hypertension was significantly augmented in KEKOs (mean arterial pressure: 146±3 mm Hg) compared with Controls (137±4 mm Hg;
MeSH term(s)	Amiloride/therapeutic use ; Angiotensin II/metabolism ; Animals ; Anti-Inflammatory Agents/therapeutic use ; Antihypertensive Agents/therapeutic use ; Dinoprostone/metabolism ; Epithelial Cells ; Epithelial Sodium Channels/genetics ; Hypertension/drug therapy ; Kidney ; Macrophages/metabolism ; Mice ; Prostaglandins ; Receptors, Prostaglandin E, EP4 Subtype/genetics ; Receptors, Prostaglandin E, EP4 Subtype/metabolism ; Sodium/metabolism ; Sodium Chloride, Dietary/metabolism
Chemical Substances	Anti-Inflammatory Agents ; Antihypertensive Agents ; Epithelial Sodium Channels ; Prostaglandins ; Receptors, Prostaglandin E, EP4 Subtype ; Sodium Chloride, Dietary ; Angiotensin II (11128-99-7) ; Amiloride (7DZO8EB0Z3) ; Sodium (9NEZ333N27) ; Dinoprostone (K7Q1JQR04M)
Language	English
Publishing date	2022-09-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.122.026581
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Article ; Online: PGE₂ promotes apoptosis induced by cytokine deprivation through EP3 receptor and induces Bim in mouse mast cells.

Kovarova, Martina / Koller, Beverly H

PloS one

2014 Volume 9, Issue 7, Page(s) e102948

Abstract: Increased mast cell numbers are observed at sites of allergic inflammation and restoration of normal mast cell numbers is critical to the resolution of these responses. Early studies showed that cytokines protect mast cells from apoptosis, suggesting a ... ...

Abstract	Increased mast cell numbers are observed at sites of allergic inflammation and restoration of normal mast cell numbers is critical to the resolution of these responses. Early studies showed that cytokines protect mast cells from apoptosis, suggesting a simple model in which diminished cytokine levels during resolution leads to cell death. The report that prostaglandins can contribute both to recruitment and to the resolution of inflammation together with the demonstration that mast cells express all four PGE2 receptors raises the question of whether a single PGE2 receptor mediates the ability of PGE2 to regulate mast cell survival and apoptosis. We report here that PGE2 through the EP3 receptor promotes cell death of mast cells initiated by cytokine withdrawal. Furthermore, the ability of PGE2 to limit reconstitution of tissues with cultured mast cells is lost in cell lacking the EP3 receptor. Apoptosis is accompanied by higher dissipation of mitochondrial potential (ΔΨm), increased caspase-3 activation, chromatin condensation, and low molecular weight DNA cleavage. PGE2 augmented cell death is dependent on an increase in intracellular calcium release, calmodulin dependent kinase II and MAPK activation. Synergy between the EP3 pathway and the intrinsic mitochondrial apoptotic pathway results in increased Bim expression and higher sensitivity of mast cells to cytokine deprivation. This supports a model in which PGE2 can contribute to the resolution of inflammation in part by augmenting the removal of inflammatory cells in this case, mast cells.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Apoptosis/physiology ; Apoptosis Regulatory Proteins/metabolism ; Bcl-2-Like Protein 11 ; Calcium/metabolism ; Cytokines/metabolism ; Dinoprostone/pharmacology ; Mast Cells/drug effects ; Mast Cells/metabolism ; Membrane Proteins/metabolism ; Mice ; Mice, Knockout ; Proto-Oncogene Proteins/metabolism ; Receptors, Prostaglandin E, EP3 Subtype/metabolism ; Signal Transduction/drug effects ; Signal Transduction/physiology
Chemical Substances	Apoptosis Regulatory Proteins ; Bcl-2-Like Protein 11 ; Bcl2l11 protein, mouse ; Cytokines ; Membrane Proteins ; Proto-Oncogene Proteins ; Receptors, Prostaglandin E, EP3 Subtype ; Dinoprostone (K7Q1JQR04M) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2014-07-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0102948
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Article ; Online: Eukaryotic phosphatase inhibitors enhance colistin efficacy in gram-negative bacteria.

Barker, William T / Jania, Leigh A / Melander, Roberta J / Koller, Beverly H / Melander, Christian

Chemical biology & drug design

2020 Volume 96, Issue 5, Page(s) 1180–1186

Abstract: The mounting threat of multi-drug-resistant (MDR) bacteria places a tremendous strain on the antimicrobial clinical arsenal, forcing physicians to revert to near-obsolete antibiotics to treat otherwise intractable infections. Antibiotic adjuvant therapy ... ...

Abstract	The mounting threat of multi-drug-resistant (MDR) bacteria places a tremendous strain on the antimicrobial clinical arsenal, forcing physicians to revert to near-obsolete antibiotics to treat otherwise intractable infections. Antibiotic adjuvant therapy has emerged as a viable alternative to the development of novel antimicrobial agents. This method uses combinations of an existing antibiotic and a non-antimicrobial small molecule, where the combination either breaks drug resistance or further potentiates antibiotic activity. Through a high-content screen of eukaryotic kinase inhibitors, our group previously identified two highly potent adjuvants that synergize with colistin, a cyclic, polycationic antimicrobial peptide that serves as a drug of last resort for the treatment of MDR Gram-negative bacterial infections. Cell signaling proteins implicated in colistin resistance mechanisms display both kinase and phosphatase activities. Herein, we explore the potential for eukaryotic phosphatase inhibitors to be repurposed as colistin adjuvants. From a panel of 48 unique structures, we discovered that the natural product kuwanon G breaks colistin resistance, while the non-antimicrobial macrolide ascomycin potentiates colistin in polymyxin-susceptible bacteria.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Colistin/pharmacology ; Drug Resistance, Multiple, Bacterial/drug effects ; Drug Synergism ; Eukaryota/enzymology ; Flavonoids/pharmacology ; Gram-Negative Bacteria/drug effects ; Gram-Negative Bacteria/growth & development ; Microbial Sensitivity Tests ; Phosphoric Monoester Hydrolases/antagonists & inhibitors ; Tacrolimus/analogs & derivatives ; Tacrolimus/pharmacology
Chemical Substances	Anti-Bacterial Agents ; Flavonoids ; kuwanon G (75629-19-5) ; immunomycin (AUF4U5NSJK) ; Phosphoric Monoester Hydrolases (EC 3.1.3.2) ; Tacrolimus (WM0HAQ4WNM) ; Colistin (Z67X93HJG1)
Language	English
Publishing date	2020-06-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2216600-2
ISSN	1747-0285 ; 1747-0277
ISSN (online)	1747-0285
ISSN	1747-0277
DOI	10.1111/cbdd.13735
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Article ; Online: Fate of arsenicals in mice carrying the human AS3MT gene exposed to environmentally relevant levels of arsenite in drinking water.

Douillet, Christelle / Miller, Madison / Cable, Peter H / Shi, Qing / El-Masri, Hisham / Matoušek, Tomáš / Koller, Beverly H / Thomas, David J / Stýblo, Miroslav

Scientific reports

2023 Volume 13, Issue 1, Page(s) 3660

Abstract: Although mice are widely used to study adverse effects of inorganic arsenic (iAs), higher rates of iAs methylation in mice than in humans may limit their utility as a model organism. A recently created 129S6 mouse strain in which the Borcs7/As3mt locus ... ...

Abstract	Although mice are widely used to study adverse effects of inorganic arsenic (iAs), higher rates of iAs methylation in mice than in humans may limit their utility as a model organism. A recently created 129S6 mouse strain in which the Borcs7/As3mt locus replaces the human BORCS7/AS3MT locus exhibits a human-like pattern of iAs metabolism. Here, we evaluate dosage dependency of iAs metabolism in humanized (Hs) mice. We determined tissue and urinary concentrations and proportions of iAs, methylarsenic (MAs), and dimethylarsenic (DMAs) in male and female Hs and wild-type (WT) mice that received 25- or 400-ppb iAs in drinking water. At both exposure levels, Hs mice excrete less total arsenic (tAs) in urine and retain more tAs in tissues than WT mice. Tissue tAs levels are higher in Hs females than in Hs males, particularly after exposure to 400-ppb iAs. Tissue and urinary fractions of tAs present as iAs and MAs are significantly greater in Hs mice than in WT mice. Notably, tissue tAs dosimetry in Hs mice resembles human tissue dosimetry predicted by a physiologically based pharmacokinetic model. These data provide additional support for use of Hs mice in laboratory studies examining effects of iAs exposure in target tissues or cells.
MeSH term(s)	Humans ; Female ; Male ; Animals ; Mice ; Arsenites ; Drinking Water ; Arsenic ; Arsenicals ; Methyltransferases
Chemical Substances	arsenite (N5509X556J) ; Arsenites ; Drinking Water ; Arsenic (N712M78A8G) ; Arsenicals ; AS3MT protein, human (EC 2.1.1.137) ; Methyltransferases (EC 2.1.1.-) ; AS3MT protein, mouse (EC 2.1.1.137)
Language	English
Publishing date	2023-03-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-30723-8
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Article ; Online: Complex Role for E-Prostanoid 4 Receptors in Hypertension.

Herrera, Marcela / Yang, Ting / Sparks, Matthew A / Manning, Michael W / Koller, Beverly H / Coffman, Thomas M

Journal of the American Heart Association

2019 Volume 8, Issue 4, Page(s) e010745

Abstract: Background Prostaglandin ... ...

Abstract	Background Prostaglandin E
MeSH term(s)	Angiotensin II/administration & dosage ; Animals ; Blood Pressure/physiology ; Dinoprostone/administration & dosage ; Disease Models, Animal ; Hypertension/drug therapy ; Hypertension/metabolism ; Hypertension/physiopathology ; Infusions, Intravenous ; Mice ; Mice, Transgenic ; Receptors, Prostaglandin E, EP4 Subtype/metabolism ; Rest ; Signal Transduction ; Vasoconstrictor Agents/administration & dosage ; Vasodilation/drug effects ; Vasodilation/physiology
Chemical Substances	Receptors, Prostaglandin E, EP4 Subtype ; Vasoconstrictor Agents ; Angiotensin II (11128-99-7) ; Dinoprostone (K7Q1JQR04M)
Language	English
Publishing date	2019-02-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.118.010745
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Article ; Online: Human ACE2 expression, a major tropism determinant for SARS-CoV-2, is regulated by upstream and intragenic elements.

Snouwaert, John N / Jania, Leigh A / Nguyen, Trang / Martinez, David R / Schäfer, Alexandra / Catanzaro, Nicholas J / Gully, Kendra L / Baric, Ralph S / Heise, Mark / Ferris, Martin T / Anderson, Elizabeth / Pressey, Katia / Dillard, Jacob A / Taft-Benz, Sharon / Baxter, Victoria K / Ting, Jenny P-Y / Koller, Beverly H

PLoS pathogens

2023 Volume 19, Issue 2, Page(s) e1011168

Abstract: Angiotensin-converting enzyme 2 (ACE2), part of the renin-angiotensin system (RAS), serves as an entry point for SARS-CoV-2, leading to viral proliferation in permissive cell types. Using mouse lines in which the Ace2 locus has been humanized by syntenic ...

Abstract	Angiotensin-converting enzyme 2 (ACE2), part of the renin-angiotensin system (RAS), serves as an entry point for SARS-CoV-2, leading to viral proliferation in permissive cell types. Using mouse lines in which the Ace2 locus has been humanized by syntenic replacement, we show that regulation of basal and interferon induced ACE2 expression, relative expression levels of different ACE2 transcripts, and sexual dimorphism in ACE2 expression are unique to each species, differ between tissues, and are determined by both intragenic and upstream promoter elements. Our results indicate that the higher levels of expression of ACE2 observed in the lungs of mice relative to humans may reflect the fact that the mouse promoter drives expression of ACE2 in populous airway club cells while the human promoter drives expression in alveolar type 2 (AT2) cells. In contrast to transgenic mice in which human ACE2 is expressed in ciliated cells under the control of the human FOXJ1 promoter, mice expressing ACE2 in club cells under the control of the endogenous Ace2 promoter show a robust immune response after infection with SARS-CoV-2, leading to rapid clearance of the virus. This supports a model in which differential expression of ACE2 determines which cell types in the lung are infected, and this in turn modulates the host response and outcome of COVID-19.
MeSH term(s)	Animals ; Humans ; Mice ; Angiotensin-Converting Enzyme 2/genetics ; COVID-19/genetics ; Mice, Transgenic ; Receptors, Virus/genetics ; SARS-CoV-2 ; Viral Tropism
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Receptors, Virus ; ACE2 protein, human (EC 3.4.17.23)
Language	English
Publishing date	2023-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011168
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