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Related Concept Videos

Hypoxia01:23

Hypoxia

1.4K
Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
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Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
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Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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Hypoglycemia and Glucagon01:15

Hypoglycemia and Glucagon

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Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
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COPD: Management Using Bronchodilators and Corticosteroids01:26

COPD: Management Using Bronchodilators and Corticosteroids

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Chronic obstructive pulmonary isease (COPD) involves a group of progressive lung disorders characterized by persistent airflow limitation and chronic respiratory symptoms. Asthma-COPD Overlap Syndrome (ACOS), encompassing features of both asthma and Chronic obstructive pulmonary disease (COPD), is a group of progressive lung disorders that includes chronic bronchitis, emphysema, and refractory (non-reversible) asthma. ACOS leads to complex clinical presentations that combine the inflammatory...
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Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

2.9K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Related Experiment Video

Updated: Oct 15, 2025

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
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Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

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Reprogramming of glucocorticoid receptor function by hypoxia.

Tineke Vanderhaeghen1,2, Steven Timmermans1,2, Deepika Watts3,4

  • 1VIB Center for Inflammation Research, Ghent, Belgium.

EMBO Reports
|October 26, 2021
PubMed
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Hypoxia alters the liver

Keywords:
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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Physiology

Background:

  • Glucocorticoid receptor (GR) signaling is crucial for hepatic function.
  • Hypoxia, a low-oxygen state, can significantly impact cellular responses.
  • Understanding GR regulation under hypoxia is vital for metabolic and inflammatory diseases.

Purpose of the Study:

  • To investigate how hypoxia affects the hepatic response to dexamethasone (DEX) mediated by the glucocorticoid receptor (GR).
  • To elucidate the molecular mechanisms underlying GR reprogramming under hypoxic conditions.

Main Methods:

  • RNA-sequencing to analyze gene expression changes.
  • Chromatin immunoprecipitation sequencing (ChIP-sequencing) to assess GR DNA-binding.
  • In vivo mouse models to study hepatic and systemic responses.

Main Results:

  • Hypoxia significantly reprograms GR activity, leading to weaker induction of classical GR-responsive genes by DEX.
  • DEX induced unique gene sets specifically under hypoxic conditions.
  • Hypoxia activates the hypothalamic-pituitary-adrenal (HPA) axis, leading to GR-dependent lipolysis and ketogenesis.
  • Hypoxia-induced HPA axis activation blunts the anti-inflammatory effect of DEX, unlike in normoxia.

Conclusions:

  • Hypoxia profoundly alters hepatic GR function and gene regulation.
  • The HPA axis plays a critical role in mediating GR responses under hypoxia.
  • These findings reveal novel pathways relevant to glucocorticoid resistance in patients.