The Open Biochemistry Journal




ISSN: 1874-091X ― Volume 13, 2019

Effects of Nerve Growth Factor and Nitric Oxide Synthase Inhibitors on Amyloid Precursor Protein mRNA Levels and Protein Stability



Janet C MacKinnon, Patricia Huether, Bettina E Kalisch*
Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, N1G 2W1, Canada

Abstract

We determined previously that nitric oxide (NO) modulates the nerve growth factor (NGF)-mediated increases in amyloid precursor protein (APP) levels in PC12 cells. To elucidate potential mechanisms, the effects of NGF and NO synthase (NOS) inhibitors on APP mRNA levels and protein stability were evaluated. Surprisingly, treatment of PC12 cells with NGF resulted in decreased levels of APP695 and APP751/770 mRNA. Therefore, the effect of NGF on APP protein stability was examined using the translation inhibitor, cycloheximide. Under these conditions, NGF did not alter the rate of APP degradation, suggesting that NGF may be enhancing the translation rate of APP. Since NOS inhibitors attenuate the NGF-mediated increase in APP levels, their effect on APP mRNA levels and protein stability was also assessed. S-methylisothiourea (S-MIU), selective for inducible NOS, decreased both APP695 and APP751/770 mRNA levels while the non-selective NOS inhibitor, Nω-nitro-L-arginine methylester (L-NAME) had no effect. In both control and NGF-treated PC12 cells, S-MIU increased the half-life of APP, with the greatest effect observed with the APP695 isoform. Based on these data we propose that in PC12 cells, NGF increases APP levels through enhanced translation rate and that NO, which modulates the NGF-induced increase in APP protein, also regulates APP mRNA levels and could play a role in APP processing.

Keywords: Amyloid precursor protein, mRNA, nerve growth factor, nitric oxide, PC12 cells, protein stability.


Article Information


Identifiers and Pagination:

Year: 2012
Volume: 6
First Page: 31
Last Page: 39
Publisher Id: TOBIOCJ-6-31
DOI: 10.2174/1874091X01206010031

Article History:

Received Date: 19/9/2011
Revision Received Date: 5/1/2012
Acceptance Date: 10/1/2012
Electronic publication date: 19/4/2012
Collection year: 2012

Article Metrics:

CrossRef Citations:
0

Total Statistics:

Full-Text HTML Views: 1846
Abstract HTML Views: 1055
PDF Downloads: 255
Total Views/Downloads: 3156

Unique Statistics:

Full-Text HTML Views: 648
Abstract HTML Views: 655
PDF Downloads: 161
Total Views/Downloads: 1464
Geographical View

© MacKinnon et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http: //creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.


* Address correspondence to this author at the Department of Biomedical Science, University of Guelph, Guelph, Ontario, N1G 2W1, Canada; Tel: 519-824-4120; Fax: 519-767-1450; E-mail: bkalisch@uoguelph.ca


Endorsements



"We have always had a fruitful cooperation and long-term experience of publishing with Bentham Open."

"A number of our original papers have appeared in its different journals, as the Bentham Open Publishers provides sufficient research in the field of science and technologies (belonging to the pharmaceutical, biotechnology, biomedical industries etc). The staff of the Bentham Open always treat our papers very seriously and gently during the rutile paper reviewing process, so far we always felt their kindness and highly cooperative support. Today, Bentham Open is providing a great support to science and research, giving opportunities of high standard publishing as well as promoting and enhancing selected papers around the world through communication and exchange of global scientific education."


Kholmirzo T. Kholmurodov
Leading Scientist
FLNP (Frank Laboratory of Neutron Physics) JINR (Joint Institute of Nuclear Research) Moscow region, Russia


Browse Contents



Webmaster Contact: info@benthamopen.net
Copyright © 2019 Bentham Open