跳至主要内容

Beta-Arrestin 1 Mediates Liver Thyrotropin Regulation of Cholesterol Conversion Metabolism via the Akt-Dependent Pathway

Author：Shaona Niu, Hui Li, Wenbin Chen, Jiajun Zhao, Ling Gao, Tao Bo   《International Journal of Endocrinology》

ABSTRACTS
After activation, G protein-coupled receptors (GPCRs) are desensitized by β-arrestins (ARRBs). Moreover, ARRBs can initiate a second wave of signaling independent of G proteins. Thyroid-stimulating hormone receptor (TSHR) is one of the GPCR members. In our previous study, TSHR was identified in the liver; the major role of TSHR in cholesterol metabolism was illustrated, as TSH could regulate hepatic cholesterol metabolism via cAMP/PKA/CREB/HMGCR and SREBP2/HNF4α/CYP7A1 pathways. It has been reported that ARRB2 predominates over ARRB1 in TSHR internalization. However, the significance of ARRBs in TSH-initiated cholesterol metabolism has not been illustrated. In our study, the effects of ARRBs on TSH-regulated cholesterol metabolism are investigated. ARRB1/2 was genetically inactivated in C57BL/6 mice and HepG2 cell line, respectively. Cholesterol levels in arrestin-knockout mice and arrestin-knockdown cells were measured. Molecules participating in cholesterol metabolism were analyzed. It turned out that deficiencies in ARRB1 led to decreased cholesterol levels and decreased TSH-stimulated AKT phosphorylation. Subsequently, the inhibitory effect on CYP7A1 by SREBP2 was reduced due to lowered mature SREBP2 level. Other than the failures of TSH in ARRB-knockdown cells, the AKT activator SC79 could enhance AKT phosphorylation and mature SREBP2 level. Our results demonstrate that ARRBs, especially ARRB1, are involved in TSH-regulated cholesterol metabolism through the AKT pathway.
SCREENSHOT

RELATED PRODUCTS
anti-SREBP2 antibodies were produced by ChinaPeptides, Suzhou, China.
CHAINING
https://www.hindawi.com/journals/ije/2018/4371396/abs/
标签：

评论

发表评论

此博客中的热门博文

The Catalytically Inactive Mutation of the Ubiquitin-Conjugating Enzyme CDC34 Affects its Stability and Cell Proliferation

Author：Xun Liu, Yang Zhang, Zhanhong Hu, Qian Li, Lu Yang,  Guoqiang Xu     《The Protein Journal》 ABSTRACTS The ubiquitin proteasome system (UPS) plays important roles in the regulation of protein stability, localization, and activity. A myriad of studies have focused on the functions of ubiquitin ligases E3s and deubiquitinating enzymes DUBs due to their specificity in the recognition of downstream substrates. However, the roles of the most ubiquitin-conjugating enzymes E2s are not completely understood except that they transport the activated ubiquitin and form E2–E3 protein complexes. Ubiquitin-conjugating enzyme CDC34 can promote the degradation of downstream targets through the UPS whereas its non-catalytic functions are still elusive. Here, we find that mutation of the catalytically active cysteine to serine (C93S) results in the reduced ubiquitination, increased stability, and attenuated degradation rate of CDC34. Through semi-quantitative proteom...
发表评论
阅读全文

Identification and Inhibitory Mechanism of Angiotensin I-Converting Enzyme Inhibitory Peptides Derived from Bovine Hemoglobin

Author：Ying Wang, Yiqun Jiang, Yongguang Yin, Jiyun Liu,  Long Ding, Jingbo Liu, Ting Zhang     《The Protein Journal》 ABSTRACTS Angiotensin I-converting enzyme (ACE, EC.3.4.15.1) inhibitory peptide is an efficacious therapy for hypertension. In this study, four dipeptides, TY, FD, FL and FG, were identified from the desalted fraction of bovine hemoglobin hydrolysate, obtained by in vitro simulated gastrointestinal digestion, via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The IC 50   value of TY and FL are 96.43?±?6.17 and 290.66?±?57.92  μM, respectively. The result of molecular docking indicated that TY occupied the ACE subsite S1 and S1′ with a lowest estimated binding energy of ?9.96  Kcal/mol, while FL occupied the subsite S5 with a lowest estimated binding energy of ?9.37  Kcal/mol. The subsite S1′ and S2′ are closer to the ACE active center (Zn 2+ ) than S5, and the lowest estimated binding energy of TY is lower ...
发表评论
阅读全文

Preparation of an antimicrobial surface by direct assembly of antimicrobial peptide with its surface binding activity

Author：Junjian Chen, Yuchen Zhu, Yancheng Song, Lin Wang,  Jiezhao Zhan, Jingcai He, Jian Zheng, Chunting Zhong, Xuetao Shi, Sa Liu, Li Ren and Yingjun Wang     《Journal of Materials Chemistry B》 ABSTRACTS Antimicrobial peptides (AMPs) are a broad prospect for clinical application against bacterial infections of biomaterials. However, a bottleneck exists as there is a lack of simple technology to prepare AMPs on biomaterials with sufficient activity, as the activity of AMP is dependent on the correct orientation on the biomaterial. In the present study, based on the conventional AMP (Tet213: KRWWKWWRRC) and surface binding peptide (SKHKGGKHKGGKHKG), we designed an Anchor-AMP that could be directly assembled onto the surface of the biomaterial and also showed excellent antimicrobial activity. By characterizing the surface using a quartz crystal microbalance with dissipation (QCM-D), contact angle, atom force microscopy (AFM) and X-ray photoelectron spectr...
发表评论
阅读全文