Key findings
- Photoaffinity cross-linking mapped the binding site on CD36 to the Asn132 to Glu177 sequence, with Met169 as the contact point, and that region overlaps the site used by oxidized low density lipoprotein. [1]
- An 84 kDa binding protein purified from rat cardiac membranes was identified by N-terminal sequencing of the deglycosylated protein as rat CD36. [2]
- In THP-1 macrophages the peptide raised ATP-binding cassette A1 and G1 transporter expression and cholesterol efflux through peroxisome proliferator-activated receptor gamma, without raising CD36 expression itself. [3]
- In 3T3-L1 adipocytes it depleted intracellular lipid content and raised cytochrome c oxidase activity and mitochondrial cristae density, again with no significant change in CD36 expression. [4]
Identity and structure
- Class
- A hexapeptide member of the growth hormone releasing peptide family [1]
- Binding partners in cited work
- The scavenger receptor CD36 in addition to growth hormone secretagogue receptor 1a, the receptor for ghrelin [1][3]
- CD36 affinity
- Reported at 2.37 micromolar in a covalent competition binding study, against 1.34 micromolar for an aza-phenylalanine analogue of GHRP-6 [5]
- Form as supplied
- Sterile lyophilized powder
Mechanism as studied
Two receptors are described in the cited work. Covalent photolabelling of CD36 followed by enzymic and chemical degradation located the binding domain at Asn132 to Glu177, and cyanogen bromide cleavage released the free ligand, pointing to Met169 as the contact residue. That domain overlaps the Gln155 to Lys183 region used by oxidized low density lipoprotein, so the authors suggest the peptide may interfere with CD36-mediated uptake of modified lipoproteins. [1]
Downstream of that binding, macrophage work linked the peptide to transcriptional activation of peroxisome proliferator-activated receptor gamma. Chromatin immunoprecipitation found receptor occupancy of the liver X receptor alpha promoter but not of the CD36 promoter, which the authors read as differential regulation of target genes rather than a general agonist profile. [3]
Research findings
In vitro
- System
- CD36 covalently photolabelled with the peptide, followed by enzymic and chemical degradation of the photoligand receptor complex
- Measured
- Identity of the photolabelled fragment and of the contact residue within the binding pocket
- Reported
- An 8 kDa photolabelled fragment corresponding to CD36 Asn132 to Glu177 was identified as the binding site. Chemical cleavage with cyanogen bromide released the free ligand, indicating Met169 as the contact point. The domain overlaps the oxidized low density lipoprotein site at Gln155 to Lys183. [1]
Ex vivo
- System
- Rat cardiac membranes labeled with a radioactive photoactivatable derivative and purified by lectin affinity chromatography and preparative gel electrophoresis, plus perfused hearts from rats, CD36-null mice and CD36-deficient spontaneously hypertensive rats
- Measured
- Apparent mass and N-terminal sequence of the binding protein, coronary perfusion pressure, CD36 expression by immunoblotting
- Reported
- A binding protein of about 84 000 relative molecular mass was identified, and the N-terminal sequence of the deglycosylated protein matched rat CD36, which was expressed in cardiomyocytes and microvascular endothelial cells. The peptide raised coronary perfusion pressure in a concentration-dependent way. That response was absent in hearts from CD36-null mice and from CD36-deficient rats, and it tracked CD36 expression. [2]
In vitro
- System
- THP-1 macrophages, with peritoneal macrophages from apolipoprotein E null and peroxisome proliferator-activated receptor gamma heterozygous mice as a comparison
- Measured
- ATP-binding cassette A1 and G1 expression, cholesterol efflux, receptor phosphorylation, promoter occupancy by chromatin immunoprecipitation
- Reported
- The peptide increased transporter expression and cholesterol efflux and raised receptor phosphorylation in THP-1 macrophages. CD36 expression did not increase. The receptor occupied the liver X receptor alpha promoter strongly but not the CD36 promoter. The response was strongly impaired in macrophages carrying only one functional receptor allele. [3]
In vitro
- System
- 3T3-L1 adipocytes, with epididymal white fat from wild type and CD36-null mice as a comparison
- Measured
- Intracellular lipid content, CD36 expression, microarray gene expression, mitochondrial cristae by electron microscopy, cytochrome c oxidase activity
- Reported
- Lipid content fell with no significant change in CD36 expression. Genes for fatty acid mobilization and oxidative phosphorylation rose, as did the thermogenic markers PGC-1 alpha and uncoupling protein 1. Cristae were intense and highly organised across the width of the mitochondria and cytochrome c oxidase activity rose. A similar mitochondrial change in mouse white fat was lost in CD36-null animals. [4]
Structural
- System
- Fifteen aza-glutamic acid analogues of GHRP-6 prepared by submonomer solid-phase synthesis and examined by circular dichroism and NMR, then competed against a radiolabeled form of the catalog peptide; the assayed ligands are azapeptides rather than the catalog peptide itself
- Measured
- Secondary structure in aqueous media and CD36 binding affinity in covalent competition
- Reported
- Depending on sequence the analogues showed random coil, polyproline type II or beta-turn spectra. Certain aza-glutamate analogues retained CD36 affinity between 2 and 27 micromolar. The catalog peptide was reported at 2.37 micromolar and an aza-phenylalanine analogue with a beta-turn conformation at 1.34 micromolar. [5]
In vitro
- System
- Neuro-2A cells exposed to hydrogen peroxide for 24 h with or without the peptide
- Measured
- Cell viability, nitrite release, morphology by skeleton and fractal analysis, caspase-3 and caspase-7 transcripts and cleaved protein, Bax and Bcl-2 transcripts, MAPK and Akt phosphorylation
- Reported
- The peptide antagonised the hydrogen peroxide damage, raising viability, reducing nitrite release and restoring normal morphology. Caspase-3 transcript and activation fell, BCL-2 family transcripts shifted, MAPK phosphorylation was inhibited and phosphorylated Akt protein rose. [6]
Handling for in-vitro work
Open questions
- No cited study compares occupancy of CD36 and of growth hormone secretagogue receptor 1a at matched concentrations, so which receptor dominates a given assay is not settled by this set.
- No cited study resolves a structure of the peptide bound to either receptor; the CD36 site is mapped by cross-linking and chemical cleavage rather than by diffraction.
Lot records
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Read a certificate of analysis ↗References
- Demers A, McNicoll N, Febbraio M, et al. Identification of the growth hormone-releasing peptide binding site in CD36: a photoaffinity cross-linking study. The Biochemical journal. 2004.
- Bodart V, Febbraio M, Demers A, et al. CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart. Circulation research. 2002.
- Avallone R, Demers A, Rodrigue-Way A, et al. A growth hormone-releasing peptide that binds scavenger receptor CD36 and ghrelin receptor up-regulates sterol transporters and cholesterol efflux in macrophages through a peroxisome proliferator-activated receptor gamma-dependent pathway. Molecular endocrinology (Baltimore, Md.). 2006.
- Rodrigue-Way A, Demers A, Ong H, et al. A growth hormone-releasing peptide promotes mitochondrial biogenesis and a fat burning-like phenotype through scavenger receptor CD36 in white adipocytes. Endocrinology. 2007.
- Sabatino D, Proulx C, Pohankova P, et al. Structure-activity relationships of GHRP-6 azapeptide ligands of the CD36 scavenger receptor by solid-phase submonomer azapeptide synthesis. Journal of the American Chemical Society. 2011.
- Meanti R, Rizzi L, Bresciani E, et al. Hexarelin Modulation of MAPK and PI3K/Akt Pathways in Neuro-2A Cells Inhibits Hydrogen Peroxide-Induced Apoptotic Toxicity. Pharmaceuticals (Basel, Switzerland). 2021.
Publication records fetched from PubMed on 2026-09-20. Profile text reviewed 2026-09-20.