Dynamic and tissue-specific proteolytic processing of chemerin in obese mice.
Dynamic and tissue-specific proteolytic processing of chemerin in obese mice.
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DOI：
10.1371/journal.pone.0202780
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Leung LLK
中科院分区：
文献类型：
--
作者：
Zhao L;Yamaguchi Y;Shen WJ;Morser J;Leung LLK
Chemerin是一种参与免疫的化学引诱物，也是一种脂肪因子，其活性受其C-末端连续蛋白水解裂解的调节。Chemerin的C-末端序列及其蛋白水解切割位点在人和小鼠之间以及在其他物种中高度保守。我们生产，纯化和表征不同的小鼠chemerin形式。Ca 2+动员试验表明，mchem 161 T和mchem 157 R的EC 50值分别为135.8 ± 158 nM和71.2 ± 55.4 nM，而mchem 156 S和mchem 155 F的效力高20倍，EC 50分别为4.6 ± 1.8 nM和3.6 ± 3.0 nM，可能代表chemerin的两种生理活性形式。未发现mchem 154 A的激动剂活性。在趋化性测定中获得了类似的结果。为了鉴定和定量生物样品中的体内小鼠chemerin形式，我们使用针对不同小鼠chemerin形式的C-末端的肽产生的抗体开发了mchem 162 K、mchem 157 R、mchem 156 S、mchem 155 F和mchem 154 A的特异性ELISA。前趋化素形式mchem 162 K是血浆中的主要趋化素形式，其增加与肥胖小鼠中总血浆趋化素的增加相匹配。在高脂饮食喂养的小鼠肥胖症发作期间，mchem 156 S在血浆中升高。相比之下，mchem 155 F是附睾脂肪提取物中的主要形式。我们的研究提供了第一个直接的证据，小鼠chemerin在体内经历了广泛的，动态的和组织特异性的蛋白水解加工，类似于人类chemerin，强调了在小鼠模型中chemerin生物学研究中测量单个chemerin形式的重要性。
Chemerin is a chemoattractant involved in immunity as well as an adipokine, whose activity is regulated by successive proteolytic cleavages at its C-terminus. Chemerin’s C-terminal sequence and its proteolytic cleavage sites are highly conserved between human and mouse, as well as in other species. We produced, purified and characterized different mouse chemerin forms. Ca2+ mobilization assay showed that the EC50 values for mchem161T and mchem157R were 135.8 ± 158 nM and 71.2 ± 55.4 nM, respectively, whereas mchem156S and mchem155F had a 20-fold higher potency with an EC50 of 4.6 ± 1.8 nM and 3.6 ± 3.0 nM, respectively, likely representing the two physiologically active forms of chemerin. No agonist activity was found for mchem154A. Similar results were obtained in a chemotaxis assay. To identify and quantify the in vivo mouse chemerin forms in biological samples, we developed specific ELISAs for mchem162K, mchem157R, mchem156S, mchem155F and mchem154A, using antibodies raised against peptides from the C-terminus of the different mouse chemerin forms. The prochemerin form, mchem162K, was the major chemerin form in plasma with its increase matching the increase of total plasma chemerin in obese mice. During the onset of obesity in high-fat diet fed mice, mchem156S was elevated in plasma. In contrast, mchem155F was the dominant form in epididymal fat extracts. Our study provides the first direct evidence that mouse chemerin undergoes extensive, dynamic and tissue-specific proteolytic processing in vivo, similar to human chemerin, underlining the importance of measuring individual chemerin forms in studies of chemerin biology in mouse models.
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DOI：
10.1093/gerona/glq078
发表时间：
2010-08-01
影响因子：
5.1
作者：
Einstein, Francine H.;Huffman, Derek M.;Muzumdar, Radhika H.
通讯作者：
Muzumdar, Radhika H.
DOI：
10.1126/science.1190816
发表时间：
2010-05-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ishibashi J;Seale P
通讯作者：
Seale P
DOI：
10.1073/pnas.0710487105
发表时间：
2008-01-08
影响因子：
11.1
作者：
Barnea, Gilad;Strapps, Walter;Lee, Kevin J.
通讯作者：
Lee, Kevin J.
影响因子：
20.3
作者：
Ge, Xiaomei;Yamaguchi, Yasuto;Morser, John
通讯作者：
Morser, John
影响因子：
4.8
作者：
Fain, JN;Madan, AK;Bahouth, SW
通讯作者：
Bahouth, SW