| Autor: |
Mattie, Michael D., Freedman, Jonathan H. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Cell Physiology; Feb2004, Vol. 286 Issue 2, pC293-C301, 9p, 2 Charts, 14 Graphs |
| Abstrakt: |
Although copper is an essential metal, it is capable of catalyzing the formation of reactive oxygen species that can cause intracellular oxidative damage. We investigated the hypothesis that metal- and oxidative stress-responsive signal transduction pathways mediate the cellular and molecular responses associated with copper exposure. Transient transfection assays using COS-7 cells and mouse metallothionein-I (MT-I) or rat NAD(P)H:oxidoreductase 1-based reporter genes demonstrate that copper activates transcription via metal and antioxidant response elements. Concomitant with copper exposures is a decrease in the level of total glutathione and an increase in oxidized glutathione. Depletion of glutathione, before copper exposure, increases metal- and oxidative stress-inducible transcription and cytotoxicity. Pretreatment with the reactive oxygen scavengers aspirin or vitamin E provides partial protection against copper toxicity and reduces inducible transcription. Experiments using signal transduction inhibitors and a metal transcription factor (MTF)-I null cell line demonstrate that copper-inducible MT-I transcription is regulated by protein kinase C and mitogen-activated protein kinase signaling pathways and requires MTF-1. The results of these studies indicate that copper activates transcription through both metal- and oxidative stress-responsive signal transduction pathways. metallothionein; signal transduction; MAPK. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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