Drak2过表达导致游离脂肪酸刺激后β细胞凋亡增加。

Drak2 overexpression results in increased beta-cell apoptosis after free fatty acid stimulation.

作者信息

Mao Jianning, Luo Hongyu, Wu Jiangping

机构信息

Laboratory of Immunology, Centre Hospitalier de l'Université de Montréal (CHUM), Notre Dame Hospital, Montreal, Quebec, Canada.

出版信息

J Cell Biochem. 2008 Nov 1;105(4):1073-80. doi: 10.1002/jcb.21910.

DOI:10.1002/jcb.21910

PMID:18777517

Abstract

Drak2 is a serine threonine kinase in the death-associated protein family. In this study, we investigated its role in free fatty acid (FFA)-induced islet apoptosis. Drak2 mRNA and protein were rapidly induced in islet beta-cells after FFA stimulation. Such Drak2 upregulation was accompanied by increased beta-cell apoptosis, which was inhibited by Drak2 knockdown using siRNA. Conversely, transgenic (Tg) Drak2 overexpression led to aggravated beta-cell apoptosis triggered by FFA. Drak2 overexpression in islets compromised the increase of anti-apoptotic factors, such as Bcl-2, Bcl-xL and Flip, upon FFA assault. Further in vivo experiments demonstrated that Drak2 Tg mice presented compromised glucose tolerance in a diet-induced obesity model. Our data show that Drak2 is detrimental to islet survival in the presence of excessive lipid.

摘要

Drak2是死亡相关蛋白家族中的一种丝氨酸苏氨酸激酶。在本研究中，我们调查了其在游离脂肪酸（FFA）诱导的胰岛细胞凋亡中的作用。FFA刺激后，胰岛β细胞中Drak2 mRNA和蛋白迅速被诱导。Drak2的这种上调伴随着β细胞凋亡增加，而使用小干扰RNA（siRNA）敲低Drak2可抑制这种凋亡。相反，转基因（Tg）过表达Drak2导致FFA引发的β细胞凋亡加剧。胰岛中Drak2过表达削弱了FFA攻击时抗凋亡因子如Bcl-2、Bcl-xL和Flip的增加。进一步的体内实验表明，在饮食诱导的肥胖模型中，Drak2转基因小鼠的糖耐量受损。我们的数据表明，在脂质过量存在的情况下，Drak2对胰岛存活有害。