Related Experiment Video
Updated: May 13, 2025
09:43
Measurement of Heme Synthesis Levels in Mammalian Cells
Published on: July 9, 2015
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HCAR2 is a novel receptor for heme
Anne Grunenwald1,2, Julie Peliconi1, Alessandra Zarantonello1
1Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale, Sorbonne Université, Université de Paris Cité, Inflammation, Complement and Cancer Team, Paris, France.
Blood Advances
|May 12, 2025
Summary
Researchers discovered Hydroxycarboxylic Acid Receptor 2 (HCAR2) as a novel sensor for extracellular heme in hemolytic diseases. This finding reveals a protective feedback loop involving HCAR2 and heme oxygenase-1 (HO-1).
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Extracellular heme from hemolysis acts as a pro-inflammatory signal in sickle cell disease (SCD) and hemolytic anemia.
- The specific receptor mediating heme's effects remained unidentified despite known GPCR signaling involvement.
Purpose of the Study:
- To identify the novel receptor responsible for sensing extracellular heme.
- To elucidate the role of this receptor in the context of hemolytic diseases.
Main Methods:
- Transcriptomic analysis (bulk RNAseq) of liver tissues from mouse models of SCD and phenylhydrazine-induced hemolysis.
- Unbiased screening of 241 G protein-coupled receptors (GPCRs).
- Functional validation using reporter cell assays, surface plasmon resonance, and absorbance spectroscopy.
Main Results:
- Hydroxycarboxylic Acid Receptor 2 (HCAR2/GPR109A), an anti-inflammatory niacin receptor, was identified as a novel heme sensor.
- HCAR2 directly binds to heme, and its expression is upregulated in the liver during hemolytic conditions.
- A negative feedback loop involving heme, HCAR2, and heme oxygenase-1 (HO-1) was uncovered.
Conclusions:
- HCAR2 is a newly discovered receptor for extracellular heme.
- The identified heme-HCAR2-HO-1 axis plays a role in tissue protection during hemolytic diseases.
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