Identification of amino‐terminal region of adiponectin as a physiologically functional domain
Identification of amino‐terminal region of adiponectin as a physiologically functional domain
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DOI：
10.1002/jcb.20779
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发表时间：
2006-05
影响因子：
4
通讯作者：
H. Ujiie;K. Oritani;H. Kato;T. Yokota;Isao Takahashi;T. Maeda;H. Masaie;M. Ichii;Y. Kamada;S. Tamura;S. Kihara;T. Funahashi;Y. Tomiyama;Y. Kanakura
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作者：
H. Ujiie;K. Oritani;H. Kato;T. Yokota;Isao Takahashi;T. Maeda;H. Masaie;M. Ichii;Y. Kamada;S. Tamura;S. Kihara;T. Funahashi;Y. Tomiyama;Y. Kanakura
脂联素是一种丰富的脂肪特异性蛋白，是一种抗糖尿病、抗动脉粥样硬化和抗炎脂肪因子。尽管通过对脂联素受体的鉴定和对其多聚化与功能之间关系的了解，脂联素领域取得了新的进展，但详细的分子背景仍不清楚。我们已建立的抗人脂联素抗体ANOC 9103和ANOC 9104阻断了脂联素的某些功能，如抑制B淋巴细胞对基质细胞的生长和抑制巨噬细胞摄取乙酰化低密度脂蛋白，提示它们可能识别脂联素的重要功能区。根据与缺失的脂联素突变体的结合能力进行表位定位，我们发现这些抗体在类胶原域开始之前识别脂联素的氨基末端区域。值得注意的是，与人脂联素17-41位氨基酸残基相对应的多肽片段(DQETTQGPGVLPLPKGACTGWMA)可以与有限类型的细胞结合，并阻断脂联素诱导的MS-5基质细胞环氧合酶-2基因的表达和前列腺素E2的产生。此外，其氨基末端区域的缺失不仅降低了抑制胶原诱导的血小板聚集的能力，也降低了抑制饮食诱导的肝脏脂肪变性的能力。这些数据表明，脂联素的氨基末端区域是一个生理功能区域，在某些类型的细胞上可能存在识别脂联素氨基末端区域的新的受体。进一步的研究将有助于理解脂联素功能的分子机制，以及设计新的治疗胰岛素抵抗、血管功能障碍和慢性炎症患者的策略。J.细胞。生物化学。2006年，98：194-207。©2006 Wiley-Liss，Inc.
Adiponectin is an abundant adipose‐specific protein, which acts as an anti‐diabetic, anti‐atherogenic, and anti‐inflammatory adipokine. Although recent advances in the field of adiponectin have been made by the identification of adiponectin receptors and by the understanding about relationship between its multimerization and functions, detailed molecular background remains unclear. Our established anti‐human adiponectin antibodies, ANOC 9103 and ANOC 9104, blocked some adiponectin functions such as the growth inhibition of B‐lymphocytes on stromal cells and the inhibition of acetylated LDL uptake in macrophages, suggesting that they may recognize important functional regions of adiponectin. As a result of epitope mapping based on the ability to bind to the deleted adiponectin mutants, we identified that these antibodies recognize amino‐terminal region of adiponectin before the beginning of the collagen‐like domain. Notably, a peptide fragment (DQETTTQGPGVLLPLPKGACTGWMA) corresponding to amino acid residues 17–41 of human adiponectin could bind to restricted types of cells and block adiponectin‐induced cyclooxygenase‐2 gene expression and prostaglandin E2 production in MS‐5 stromal cells. Moreover, the deletion of its amino‐terminal region reduced the abilities to inhibit not only collagen‐induced platelet aggregation but also diet‐induced hepatic steatosis. These data indicate that amino‐terminal region of adiponectin is a physiologically functional domain and that a novel receptor, which recognizes amino‐terminal region of adiponectin, may exist on some types of cells. Further investigations will contribute to the understanding of molecular mechanisms about adiponectin functions as well as to the designing of novel strategies for the treatment of patients with insulin‐resistance, vascular dysfunction, and chronic inflammation. J. Cell. Biochem. 98: 194–207, 2006. © 2006 Wiley‐Liss, Inc.