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Chemerin‐Derived Peptide C ‐20 Suppressed Gonadal Steroidogenesis
Author(s) -
Li Lei,
Huang Chen,
Zhang Xu,
Wang Jiangbo,
Ma Ping,
Liu Yongjun,
Xiao Tianxia,
Zabel Brian A.,
Zhang Jian V.
Publication year - 2014
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12164
Subject(s) - chemerin , chemotaxis , receptor , internalization , chemotaxis assay , chemokine , biology , hek 293 cells , endocrinology , microbiology and biotechnology , chemistry , medicine , biochemistry , adipokine , insulin resistance , insulin
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 ( CMKLR 1)/ HEK 293 transfectants and G protein‐coupled receptor 1 ( GPR 1)/ HEK 293 transfectants. In vitro transwell chemotaxis assay in CMKLR 1/ L 1.2 transfectants, primary L eydig cell culture, and antral follicle culture was explored to investigate the bioactivity of C ‐20. Results C ‐20 bound to chemerin receptors CMKLR 1 and GPR 1 with high affinity triggered CMKLR 1 internalization and stimulated subsequent signal C ‐ FOS expression and c AMP production. C ‐20, such as chemerin, showed CMKLR 1‐dependent chemotactic property. Furthermore, in primary L eydig 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 CMKLR 1 and GPR 1 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/ CMKLR 1 and chemerin/ GPR 1 signaling.