Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hepatic BMAL1 and HIF1a regulate a time-dependent hypoxic response and their absence leads to Hepatopulmonary Syndrome II

ABSTRACT: The transcriptional response to hypoxia is temporally regulated yet the molecular underpinnings and physiological implications are unknown. We examined herein the roles of hepatic Bmal1 and Hif1a in the circadian response to hypoxia in mice. We found that the majority of the transcriptional response to hypoxia is dependent on Bmal1 or Hif1a, through shared and distinct roles that are daytime determined. We further show that HIF1a accumulation upon hypoxia is temporally regulated and Bmal1-dependent. Unexpectedly, mice lacking both hepatic Bmal1 and Hif1a are hypoxemic and exhibit increased mortality upon hypoxic exposure in a daytime-dependent manner. These mice display mild liver dysfunction with pulmonary vasodilation likely due to ERK activation, endothelial nitric oxide synthase and nitric oxide accumulation in lungs, suggestive of hepatopulmonary syndrome. Our findings indicate that hepatic BMAL1 and HIF1a are key time-dependent regulators of the response to hypoxia and provide molecular insight on the pathophysiology of hepatopulmonary syndrome.

ORGANISM(S): Mus musculus

PROVIDER: GSE254438 | GEO | 2024/05/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hepatic BMAL1 and HIF1a regulate a time-dependent hypoxic response and their absence leads to Hepatopulmonary Syndrome

Project description:The transcriptional response to hypoxia is temporally regulated yet the molecular underpinnings and physiological implications are unknown. We examined herein the roles of hepatic Bmal1 and Hif1a in the circadian response to hypoxia in mice. We found that the majority of the transcriptional response to hypoxia is dependent on Bmal1 or Hif1a, through shared and distinct roles that are daytime determined. We further show that HIF1a accumulation upon hypoxia is temporally regulated and Bmal1-dependent. Unexpectedly, mice lacking both hepatic Bmal1 and Hif1a are hypoxemic and exhibit increased mortality upon hypoxic exposure in a daytime-dependent manner. These mice display mild liver dysfunction with pulmonary vasodilation likely due to ERK activation, endothelial nitric oxide synthase and nitric oxide accumulation in lungs, suggestive of hepatopulmonary syndrome. Our findings indicate that hepatic BMAL1 and HIF1a are key time-dependent regulators of the response to hypoxia and provide molecular insight on the pathophysiology of hepatopulmonary syndrome.

2024-05-08 | GSE254219 | GEO

Genome-wide analysis of HIF1A and ARNT binding in N1E115 cells

Project description:Neuronal nitric oxide synthase 1 (NOS1) produces the gaseous signaling molecule nitric oxide (NO), which plays important roles in the development and function of the nervous system. The regulation of Nos1 gene expression is incompletely understood. Here, we explored the role of physiological hypoxia in the control of Nos1 transcription and the underlying mechanisms using N1E115 mouse neuroblastoma cells as a model. N1E115 cells were cultured for 3 days at high (20%) and low (4%) oxygen levels. Following the verification of upregulation of Nos1 mRNA and protein levels in response to 4% oxygen, we analyzed HIF1A and ARNT binding by chromatin immunoprecipitation-sequencing.

2024-02-14 | GSE139477 | GEO

Oleic acid-dependent modulation of Nitric Oxide Associated 1 protein levels regulate nitric oxide mediate signaling in plant defense.

2012-08-01 | GSE36797 | GEO

Oleic acid-dependent modulation of Nitric Oxide Associated 1 protein levels regulate nitric oxide mediate signaling in plant defense.

Project description:Oleic acid-dependent modulation of Nitric Oxide Associated 1 protein levels regulate nitric oxide- mediate signaling in plant defense. Nitric Oxide, Oleic acid, Salicylic acid, Arabidopsis, Defense Wild-type Col-0, mutant genotypes ssi2, ssi2 act1 and ssi2 sid2 with three biological replicates were analyzed (one array each)

2012-07-31 | E-GEOD-36797 | biostudies-arrayexpress

Proteomic profile of two different cerebral hypoxic models treated with antioxidant melatonin and nitric oxide donors

Project description:In the present work we analyse the proteomic profile of two models of cerebral hypoxia with different severity as well as their response after treatment with the antioxidant melatonin and the nitric oxide-donor isosorbide mononitrate (ISMN).

2017-07-17 | PXD004091 | Pride

Effect of NO-sulindac treatment on hypoxic prostate cancer cells

Project description:The hypoxia response contributes to radio and chemo-resistance in cancer cells. Our previous work has shown that the nitric oxide donating non-steroidal anti-inflammatory drug (NO-NSAID) NO-sulindac is a potent inhibitor of the hypoxia response in prostate cancer cells and leads to increased susceptibilty to radiation. In this study we used microarrays to investigated the global impact of NO-sulindac on the hypoxia response in prostate cancer cells with a view to determining the mechanism of action.

2012-12-01 | GSE34112 | GEO

Transcriptome response to nitric oxide in Pseudomonas aeruginosa

Project description:DNA microarray analysis was employed to investigate the transcriptome response to nitric oxide in Pseudomonas aeruginosa. We focused on the role played by the nitric oxide-response regulators DNR and FhpR and an oxygen-response regulator ANR in the response. The transcriptome profiles of the P. aeruginosa strains before and after exposure to nitric oxide under the microaerobic conditions were analyzed. Wild type, its anr, dnr, and fhpR mutants, and the anr mutant that express dnr were used for the analyses. Pseudomonas aeruginosa wild type (PAO1ut), anr mutant (RManr), dnr mutant (RMdnr), anr mutant that constitutively expresses DNR (RManrEXdnr), and fhpR mutant (PDM2665) were cultivated microaerobically in LB in 1-liter jar fermenter. When optical density at 600 nm reached 0.3, nitric oxide-saturated water was added to the medium (final nitric oxide concentration was 20 micro-M). RNA was isolated from a 10 ml aliquot of the culture prior to the addition of nitric oxide and at 5 min after the addition. The experiment was performed in duplicate independent cultures.

2014-12-08 | E-GEOD-58862 | biostudies-arrayexpress

Chromosome conformation analysis of N1E115 cells by HiC

2024-02-14 | GSE139470 | GEO

Transcriptome analysis of N1E115 cells cultured in the presence of 20% or 4% O2

Project description:Neuronal nitric oxide synthase 1 (NOS1) produces the gaseous signaling molecule nitric oxide (NO), which plays important roles in the development and function of the nervous system. The regulation of Nos1 gene expression is incompletely understood. Here, we explored the role of physiological hypoxia in the control of Nos1 transcription and the underlying mechanisms using N1E115 mouse neuroblastoma cells as a model. N1E115 cells were cultured for 3 days at high (20%) and low (4%) oxygen levels. Following the verification of upregulation of Nos1 mRNA and protein levels in response to 4% oxygen, we performed transcriptome analysis using stranded total RNA-sequencing.

2024-02-14 | GSE139472 | GEO

Project description:Nitric oxide-dependent anaerobic ammonium oxidation

| PRJNA485513 | ENA