Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-51633

Nishina, A; Kimura, H; Kozawa, K; Sommen, G L; Nakamura, T; Heimgartner, H; Koketsu, M; Furukawa, S (2011). A superoxide anion-scavenger, 1,3-selenazolidin-4-one suppresses serum deprivation-induced apoptosis in PC12 cells by activating MAP kinase. Toxicology and Applied Pharmacology, 257(3):388-395.

[img]Published Version
PDF - Registered users only
803kB

View at publisher
[img]
Preview
Accepted Version
PDF
304kB

Abstract

Synthetic organic selenium compounds, such as ebselen, may show glutathione peroxidase-like antioxidant activity and have a neurotrophic effect. We synthesized 1,3-selenazolidin-4-ones, new types of synthetic organic selenium compounds (five-member ring compounds), to study their possible applications as antioxidants or neurotrophic-like molecules. Their superoxide radical scavenging effects were assessed using the quantitative, highly sensitive method of real-time kinetic chemiluminescence. At 166 μM, the O2− scavenging activity of 1,3-selenazolidin-4-ones ranged from 0 to 66.2%. 2-[3-(4-Methoxyphenyl)-4-oxo-1,3-selenazolidin-2-ylidene]malononitrile (compound b) showed the strongest superoxide anion-scavenging activity among the 6 kinds of 2-methylene-1,3-selenazolidin-4-ones examined. Compound b had a 50% inhibitory concentration (IC50) at 92.4 μM and acted as an effective and potentially useful O2− scavenger in vitro. The effect of compound b on rat pheochromocytome cell line PC12 cells was compared with that of ebselen or nerve growth factor (NGF) by use of the MTT [3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay. When ebselen was added at 100 μM or more, toxicity toward PC12 cells was evident. On the contrary, compound b suppressed serum deprivation-induced apoptosis in PC12 cells more effectively at a concentration of 100 μM. The activity of compound b to phosphorylate mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) 1/2 (MAP kinase) in PC12 cells was higher than that of ebselen, and the former at 100 μM induced the phosphorylation of MAP kinase to a degree similar to that induced by NGF. From these results, we conclude that this superoxide anion-scavenger, compound b, suppressed serum deprivation-induced apoptosis by promoting the phosphorylation of MAP kinase.

Citations

3 citations in Web of Science®
3 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

43 downloads since deposited on 06 Dec 2011
16 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
DDC:540 Chemistry
Language:English
Date:15 December 2011
Deposited On:06 Dec 2011 08:06
Last Modified:13 Jul 2014 19:43
Publisher:Elsevier
ISSN:0041-008X
Publisher DOI:10.1016/j.taap.2011.09.022
PubMed ID:22001386

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page