A novel neuroprotective role of a small peptide from flesh fly, 5-S-GAD in the rat retina in vivo.

フォーマット:

論文

責任表示:

Koriyama, Yoshiki ; Tanii, Hideji ; Ohno, Mamoru ; Kimura, Takahito ; Kato, Satoru

言語:

英語

出版情報:

Elsevier, 2008-11-01

著者名:

• Koriyama, Yoshiki
• Tanii, Hideji
• Ohno, Mamoru
• Kimura, Takahito
• Kato, Satoru

掲載情報:

Brain Research

ISSN:

0006-8993      

巻:

1240

開始ページ:

196

終了ページ:

203

バージョン:

author

概要:

金沢大学医薬保健研究域　医学系<br />N-β-Alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD), an antibacterial substance isolated from flesh fly, has been described as having multipotential biological activities toward various tissues. … However, there has been no report testing its action on neural cells. In the present study, we investigate whether 5-S-GAD is neurotoxic or neuroprotective to the rat retina. 5-S-GAD at high doses (more than 200 pmol) induced apoptosis of retinal neurons 7 days after intraocular injection. 5-S-GAD at low doses (2-20 pmol) significantly attenuated the loss of retinal ganglion cells (RGCs) and the thinning of inner retina induced by NMDA in a dose-dependent manner. To understand the protective mechanism of 5-S-GAD, we investigated the influence of 5-S-GAD on the cell survival molecules, phospho-Akt and Bcl-2. 5-S-GAD (2-20 pmol) rapidly increased phospho-Akt expression 1-7 days and Bcl-2 expression 3-7 days after injection. The cellular localization of this increase was both in bipolar cells and RGCs. This neurosurvival effect of 5-S-GAD was further tested using another model of optic nerve injury. 5-S-GAD significantly blocked the apoptosis of RGCs 7 days after optic nerve crush. These results show that 5-S-GAD (2-20 pmol) protects against the NMDA- and optic nerve crush-induced apoptosis of RGCs. The neuroprotective action of 5-S-GAD in the retina might be mediated by the cell survival phospho-Akt/Bcl-2 system and offers a therapeutic option to rescue RGCs from various types of excitotoxic disease, such as glaucoma. © 2008 Elsevier B.V. All rights reserved. 続きを見る

URL:

http://hdl.handle.net/2297/11954