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Axonal Protection by 17{beta}-Estradiol through Thioredoxin-1 in Tumor Necrosis Factor-Induced Optic Neuropathy.
MedLine Citation:
PMID:  21586560     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Axonal degeneration often leads to the death of neuronal cell bodies. Previous studies demonstrated the substantial protective role of 17β-estradiol (E2) in several types of neuron. However, most studies examined cell body protection, and the role of 17β-E2 in axonal degeneration of retinal ganglion cells (RGC) remains unclear. In this study, we showed the presence of thioredoxin-1 (Trx1) in the optic nerve axons and found that the levels of Trx1 protein were significantly decreased in isolated RGC and the optic nerve after intravitreal injection of TNF, which was shown previously to induce optic nerve degeneration and subsequent loss of RGC. These changes were concomitant with disorganization of the microtubules with neurofilament accumulation, which were blocked by 17β-E2 implantation. 17β-E2 treatment also totally abolished TNF-induced decreases in Trx1 protein levels in isolated RGC and the optic nerve. The induction of Trx1 by 17β-E2 in the optic nerve was significantly inhibited by simultaneous injection of Trx1 small interfering RNA (siRNA) with TNF. Up-regulation of Trx1 by 17β-E2 in RGC-5 cells was prevented by Trx1 siRNA treatment. 17β-E2 significantly prevented TNF-induced axonal loss, and this axonal-protective effect was inhibited by intravitreal injection of Trx1 siRNA. This finding was also supported by the quantification of microtubules and neurofilaments. These results suggest that a Trx1 decrease in RGC bodies and their axons may be associated with TNF-induced optic nerve axonal degeneration. Axonal protection by 17β-E2 may be related to its regulatory effect on Trx1 induction.
Authors:
Yasushi Kitaoka; Yasunari Munemasa; Yasuhiro Hayashi; Junko Kuribayashi; Natsuko Koseki; Kaori Kojima; Toshio Kumai; Satoki Ueno
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-17
Journal Detail:
Title:  Endocrinology     Volume:  -     ISSN:  1945-7170     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Departments of Ophthalmology (Y.K., Y.M., Y.H., J.K., K.K., S.U.) and Pharmacology (T.K.), St. Marianna University School of Medicine, Kawasaki, 216-8511, Kanagawa, Japan; and Department of Life Sciences (N.K.), Toyo University, Oura, 374-0193 Gunma, Japan.
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