Expression of peptide NAP in rat retinal Muller cells prevents hypoxia-induced retinal injuries and promotes retinal neurons growth

被引：21
作者：
Zheng, Yuping [1 ]
Zeng, Hao [2 ]
She, Huaning [1 ]
Liu, Hui [1 ]
Sun, Naixue [1 ]
机构：
[1] Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 2, Dept Ophthalmol, Xian 710004, Shaanxi, Peoples R China
[2] St Vincent Hosp, Dept Pathol, Worcester, MA 01608 USA
来源：
BIOMEDICINE & PHARMACOTHERAPY | 2010年 / 64卷 / 06期
基金：
中国国家自然科学基金;
关键词：
Neuroprotective peptide; NAP; Gene fusion; Hypoxia; MEDIATED GENE-TRANSFER; GANGLION-CELLS; GLIAL-CELLS; IN-VITRO; PROTEIN; NEUROPROTECTION; ASTROCYTES; ADENOVIRUS; SURVIVAL; RABBIT;
D O I：
10.1016/j.biopha.2010.01.016
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
NAP (NAPVSIPQ) is a short peptide derived from activity-dependent neuroprotective protein (ADNP) sequence, whose potent and direct neuroprotective capabilities have been widely accepted. However, due to the high risk and inconvenience of intraocular injections. NAP is difficult to be clinically administered as therapeutic agent in treating retinal diseases. Currently, stable transfection of this octapeptide into cells has not been reported, partly because of its small size and lacking of 5' signal sequence Here, we have developed a novel NT4-NAP fusion gene by attaching the 5' nonfunctional preproregion of neurotrophin 4 (NT4) to NAP cDNA. Recombinant adeno-associated virus was established to introduce NT4-NAP construct into cultured rat retinal Muller cells (RMC), resulting in sustained high level NAP production from stable transfection. Functional analyses of RMC cells transfected with NAP revealed the remarkably reduced cytotoxicity and apoptosis of the cells under hypoxia. Furthermore, coculturing of transfected RMC-NAP cells with primary rat retinal neural cells offer marked protection to the latter against hypoxia induced cellular damages. Together our data indicate that stable transfection of NAP into retinal Muller cells with constant NAP production is possible. NAP produced from cellular transfection maintained its biological neuroprotective activities This targeted gene expression may provide an effective treatment for retinal diseases in the near future. Crown Copyright (C) 2010 Published by Elsevier Masson SAS All rights reserved
引用
收藏
页码：417 / 423
页数：7
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