Nitric oxide induces the synthesis of glutathione and protects endothelial cells towards hydrogen peroxide via "free" zinc
Cortese-Krott, MM; Suschek, CV; Wetzel, W; Kroncke, KD; Kolb-Bachofen, V
HERO ID
975884
Reference Type
Journal Article
Subtype
Abstract
Year
2008
Language
English
| HERO ID | 975884 |
|---|---|
| Material Type | Abstract |
| In Press | No |
| Year | 2008 |
| Title | Nitric oxide induces the synthesis of glutathione and protects endothelial cells towards hydrogen peroxide via "free" zinc |
| Authors | Cortese-Krott, MM; Suschek, CV; Wetzel, W; Kroncke, KD; Kolb-Bachofen, V |
| Journal | Free Radical Biology and Medicine |
| Volume | 45 |
| Issue | Suppl. |
| Page Numbers | S112-S112 |
| Abstract | We have recently shown that zinc increases the synthesis of the antioxidant glutathione (GSH) by increasing the expression of the catalytic subunit of glutamate cysteine ligase (GCLC), the rate-limiting enzyme of GSH de novo biosynthesis, and in this way protects endothelial cells (EC) against H2O2-induced toxicity [1]. High output nitric oxide (NO) synthesis induces zinc release from proteins containing zinc sulfur clusters and, similarly to zinc, protects EC against H2O2-induced toxicity. Thus, in the present study we investigated whether “free” zinc released by NO within the cells plays a signaling role in the NO-mediated protection against H2O2 in EC. We found that the NO-mediated protection towards H2O2 depends on the NO-mediated increase of GSH via inducing the expression of GCLC. Chelating intracellular “free” zinc abrogates the NO-mediated increase of GCLC and of cellular GSH levels. As a consequence, the NO-mediated protection against H2O2-induced toxicity is impaired. We also show that under pro-inflammatory conditions both inhibition of endogenous NO synthesis and chelation of intracellular “free” zinc decreases the cellular GSH levels and increases the H2O2-induced toxicity. By using RNA interference and confocal microscopy we found that NO-induced expression of GCLC is dependent on the activation of the transcription factor Nrf2. These findings show that intracellular “free” zinc plays a signaling role in the protective activity of NO, and could explain why maintenance of an adequate zinc status in the endothelium is important to protect from oxidative stress and the development of vascular disease. [1] Cortese, M. M.; Suschek, C. V.; Wetzel, W.; Kröncke, K. D.; Kolb-Bachofen, V. Zinc protects endothelial cells from hydrogen peroxide via Nrf2-dependent stimulation of glutathione biosynthesis. Free Radic Biol Med 44:2002-2012; 2008. |
| Wosid | WOS:000260867900318 |
| Url | http://www.sciencedirect.com/science/article/pii/S089158490800628X |
| Is Certified Translation | No |
| Dupe Override | No |
| Conference Location | Indianapolis, IN |
| Conference Name | Society for Free Radical Biology and Medicine 15th Annual Meeting |
| Conference Date | November 19-23, 2008 |
| Is Public | Yes |
| Language Text | English |
| Relationship(s) |
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