Evidence for synergistic action of transthyretin and IGF-I over the IGF-I receptor

被引：8
作者：
Vieira, Marta [1 ]
Leal, Sonia S. [2 ,3 ,4 ]
Gomes, Claudio M. [2 ,3 ,4 ]
Saraiva, Maria Joao [1 ]
机构：
[1] Univ Porto, Inst Invest & Inovacao Saude I3S, Unidade Neurobiol Mol, IBMC, Rua Campo Alegre 823, P-4100 Oporto, Portugal
[2] Univ Nova Lisboa, Inst Tecnol Quim & Biol, P-2780157 Oeiras, Portugal
[3] Univ Lisbon, Biosyst & Integrat Sci Inst, Fac Ciencias, P-1749016 Lisbon, Portugal
[4] Univ Lisbon, Dept Chem & Biochem, P-1749016 Lisbon, Portugal
来源：
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2016年 / 1862卷 / 04期
关键词：
Ischemia; Glutamate; Synergy; Protein-protein interaction; GROWTH-FACTOR-I; TRANSCRIPTION FACTOR; CHOROID-PLEXUS; ALZHEIMERS-DISEASE; THYROXINE-BINDING; CELL-SURVIVAL; INSULIN; BRAIN; SERUM; AKT;
D O I：
10.1016/j.bbadis.2016.01.008
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Transthyretin (TTR) has a neuroprotective role in the central nervous system (CNS) in Alzheimer's disease (AD) and cerebral ischemia. Increased levels of TTR and activated insulin-like growth factor I receptor (IGF-IR) are associated with reduced neurodegeneration in an AD mouse model. In the present study, we found that TTR and IGF-I have a synergistic effect on activation of one of the IGF-IR signaling pathways. Hippocampus of TTR null mice present decreased levels of phosphorylated IGF-IR and Akt when compared with TTR wild type littermate animals. Cell studies reveal the synergistic effect of TTR and IGF-I in promoting IGF-IR signaling even under glutamate induced toxicity. TTR:IGF-IR complexes are identified and a bio-layer interferometry assay demonstrated an interaction between TTR and IGF-IR with a K-D ranging from 99 to 744 nM. In summary, our results point to a new TTR role through the IGF-I axis, mediated through TTR-IGF-IR interactions. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码：797 / 804
页数：8
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