Chemerin-derived peptide C-20 suppressed gonadal steroidogenesis.

Chemerin-derived peptide C-20 suppressed gonadal steroidogenesis.
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凯莫瑞衍生肽 C-20 抑制性腺类固醇生成。

DOI:
10.1111/aji.12164
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发表时间:
2014-03
期刊:
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子:
--
通讯作者:
Zhang JV
Zhang JV
中科院分区:
其他
文献类型:
--
作者:
Li L;Huang C;Zhang X;Wang J;Ma P;Liu Y;Xiao T;Zabel BA;Zhang JV

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Chemerin是一种新型的化学引诱剂和脂肪因子,参与白细胞募集、炎症、脂肪生成、脂质/碳水化合物代谢和生殖。基于生物信息学搜索的推定小肽的保守区域的pre-pro-chemerin,进化的保守区域两侧的潜在的转化酶切割位点,我们确定了它命名为C-20。本实验研究了C-20与chemerin受体的结合能力及其潜在的生物活性。在CMKLR 1/HEK 293和GPR 1/HEK 293转染细胞中进行放射配体结合试验、受体内化试验和早期反应基因C-FOS模拟试验、cAMP试验。采用体外transwell趋化实验、原代睾丸间质细胞培养和窦状卵泡培养等方法研究C-20的生物学活性。C-20以高亲和力与chemerin受体CMKLR 1和GPR 1结合,触发CMKLR 1内化并刺激随后的信号C-FOS表达和cAMP产生。C-20,如chemerin,表现出CMKLR 1依赖的趋化特性。此外,在初级Leydig细胞和窦状卵泡,C-20显示类似的,但较弱的抑制作用,人绒毛膜促性腺激素刺激的睾酮和孕酮的生产,与chemerin相比。新的chemerin衍生的C-20肽结合chemerin受体CMKLR 1和GPR 1,并表现出类似的,但不太有效的生物活性的趋化性和性腺类固醇合成的抑制,表明优化后,C-20可能是一个有用的实验工具,为理解chemerin/CMKLR 1和chemerin/GPR 1信号转导的生物学功能。
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. 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. 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. 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.
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