Chemerin-derived peptide C-20 suppressed gonadal steroidogenesis.

Abstract

PROBLEM:

Chemerin is a novel chemo-attractant and adipokine involved in leukocyte recruitment, inflammation, adipogenesis, lipid/carbohydrate metabolism, and reproduction. Based on the bioinformatic search for putative small peptides in the conserved region of pre-pro-chemerin, an evolutionary conserved region flanked by potential convertase cleavage sites was identified and we named it as C-20. The binding capacity of C-20 to chemerin receptors and its potential bioactivities were investigated in this study.

METHOD OF STUDY:

Radioligand binding assay, receptor internalization assay, and early response gene C-FOS simulation, cAMP assay were carried out in chemokine-like receptor 1 (CMKLR1)/HEK293 transfectants and G protein-coupled receptor 1 (GPR1)/HEK293 transfectants. In vitro transwell chemotaxis assay in CMKLR1/L1.2 transfectants, primary Leydig cell culture, and antral follicle culture was explored to investigate the bioactivity of C-20.

RESULTS:

C-20 bound to chemerin receptors CMKLR1 and GPR1 with high affinity triggered CMKLR1 internalization and stimulated subsequent signal C-FOS expression and cAMP production. C-20, such as chemerin, showed CMKLR1-dependent chemotactic property. Furthermore, in primary Leydig cells and antral follicles, C-20 showed similar but less potent suppressive effect on human chorionic gonadotropin-stimulated testosterone production and progesterone production, compared with chemerin.

CONCLUSION:

The novel chemerin-derived C-20 peptide binds to chemerin receptors CMKLR1 and GPR1 and showed similar but less potent bioactivity in chemotaxis and the suppression of gonadal steroidogenesis, suggesting that after optimization, C-20 is possible to be a useful experimental tool for the understanding of the biological functions of chemerin/CMKLR1 and chemerin/GPR1 signaling.

• Authors: Lei Li, Chen Huang, Xu Zhang, Jiangbo Wang, Ping Ma, Yongjun Liu, Tianxia Xiao, Brian A Zabel, Jian V Zhang
• Journal: American journal of reproductive immunology (New York, N.Y. : 1989) (Am J Reprod Immunol) Vol. 71 Issue 3 Pg. 265-77 (Mar 2014) ISSN: 1600-0897 [Electronic] Denmark
• PMID: 24506805 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• CMKLR1 protein, human
• Chimerin Proteins
• GPR1 protein, human
• Peptide Fragments
• Proto-Oncogene Proteins c-fos
• Receptors, Chemokine
• Receptors, G-Protein-Coupled
• chemerin-derived peptide C-20
• Testosterone
• Progesterone
• Cyclic AMP

Topics

• Chemotaxis
• Chimerin Proteins (genetics, metabolism)
• Computational Biology
• Cyclic AMP (metabolism)
• HEK293 Cells
• Humans
• Leydig Cells
• Male
• Peptide Fragments (genetics, metabolism)
• Progesterone (biosynthesis)
• Protein Binding
• Proto-Oncogene Proteins c-fos (genetics, metabolism)
• Receptors, Chemokine (genetics, metabolism)
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Signal Transduction
• Testis (physiology)
• Testosterone (biosynthesis)