机构：[a]Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA[b]Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA[c]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China神经内科首都医科大学宣武医院
Recent studies recognize that Hypocretin system (also known as Orexin) plays a critical role in sleep/wake disorders and feeding behaviors. However, little is known about the regulation of the Hypocretin system. It is also known that tumor necrosis factor alpha (TNF-alpha) is involved in the regulation of sleep/wake cycle. Here, we test our hypothesis that the Hypocretin system is regulated by TNF-alpha. Prepro-Hypocretin and Hypocretin receptor 2 (HcrtR2) can be detected at a very low level in rat B35 neuroblastoma cells. In response to TNF-alpha, Prepro-Hypocretin mRNA and protein levels are down-regulated, and also HcrtR2 protein level is down-regulated in B35 cells. To investigate the mechanism, exogenous rat Prepro-Hypocretin and rat HcrtR2 were overexpressed in B35 cells. In response to TNF-alpha, protein and mRNA of Prepro-Hypocretin are significantly decreased (by 93% and 94%. respectively), and the half-life of Prepro-Hypocretin mRNA is decreased in a time- and dose-dependent manner. The level of HcrtR2 mRNA level is not affected by TNF-alpha treatment; however, HcrtR2 protein level is significantly decreased (by 86%) through ubiquitination in 835 cells treated with TNF-alpha. Downregulation of cellular inhibitor of apoptosis protein-1 and -2 (cIAP-1 and -2) abrogates the HcrtR2 ubiquitination induced by TNF-alpha. The control green fluorescent protein (GFP) expression is not affected by TNF-alpha treatment. These studies demonstrate that TNF-alpha can impair the function of the Hypocretin system by reducing the levels of both Prepro-Hypocretin and HcrtR2. (C) 2010 Elsevier B.V. All rights reserved.
基金：
awards from NIH/NHLBI grants HL085324 and HL095451 (Q.D.), and from the American Heart Association, Greater Southeast Affiliate Research Program (G.Q.C.).
第一作者机构：[a]Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA[c]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China[*2]Department of Neurology, Xuanwu Hospital, No. 45 Changchun St., Beijing, China.
通讯作者：
通讯机构：[*1]Department of Medicine, University of Alabama at Birmingham, 1900 University Boulevard, THT 422, Birmingham, AL 35294, USA.[*2]Department of Neurology, Xuanwu Hospital, No. 45 Changchun St., Beijing, China.
推荐引用方式(GB/T 7714)：
Shuqin Zhan,Guo-Qiang Cai,Anni Zheng,et al.Tumor necrosis factor-alpha regulates the Hypocretin system via mRNA degradation and ubiquitination[J].BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE.2011,1812(4):565-571.doi:10.1016/j.bbadis.2010.11.003.
APA：
Shuqin Zhan,Guo-Qiang Cai,Anni Zheng,Yuping Wang,Jianping Jia...&Qiang Ding.(2011).Tumor necrosis factor-alpha regulates the Hypocretin system via mRNA degradation and ubiquitination.BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,1812,(4)
MLA：
Shuqin Zhan,et al."Tumor necrosis factor-alpha regulates the Hypocretin system via mRNA degradation and ubiquitination".BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 1812..4(2011):565-571
