期刊
NEUROBIOLOGY OF DISEASE
卷 38, 期 3, 页码 446-455出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2010.03.005
关键词
Trx; Tubby; Retina; Degeneration; Oxidative stress; Neurotrophins; Neuroprotection; Survival; Apoptosis; Transgene
资金
- Foundation Fighting Blindness (FFB) [C-NP-0707-0404-UOK08, FFB TA-NP-1107-0434-UOK]
- NIH [R21EY018306, R01EY018724 COBRE/Core P20 RR17703, NEI/Core P30- EY12190, EY014427]
- Research to Prevent Blindness, New York, NY
- RPB
The Tubby mouse is a phenotypic model for sensorineural deafness and retinal dystrophy including Usher syndrome type 1. Thioredoxin is a small 13 kDa protein which, when ubiquitously expressed as a transgene in the mouse, provides protection against multiple disease states including light-induced and oxidative stress-induced neurodegeneration and is down-regulated in the Tubby retina. We tested if overexpression of human thioredoxin in the Tubby mouse inhibits retinal degeneration and loss of visual function. Electroretinography, immunocytochemistry, quantitative histology, RT-PCR and Western blots were used to obtain data which showed that thioredoxin overexpression prevented loss of photoreceptors and retinal function. Analysis of signal pathways showed that thioredoxin up-regulated neurotrophic factors BDNF and GDNF and activated survival signaling pathways Akt, Ras/Raf1 / and the ERKs while inhibiting the ASK1/JNK apoptosis pathway. Relationships between the Tubby gene, its pathological phenotype and regulation of the thioredoxin system remain to be established. (C) 2010 Elsevier Inc. All rights reserved.
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