The C-terminal proteolytic processing of extracellular superoxide dismutase is redox regulated.
Free Radic Biol Med
; 52(1): 191-7, 2012 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-22062630
ABSTRACT
The antioxidant protein extracellular superoxide dismutase (EC-SOD) encompasses a C-terminal region that mediates interactions with a number of ligands in the extracellular matrix (ECM). This ECM-binding region can be removed by limited proteolysis before secretion, thus supporting the formation of EC-SOD tetramers with variable binding capacity. The ECM-binding region contains a cysteine residue (Cys219) that is known to be involved in an intersubunit disulfide bridge. We have determined the redox potential of this disulfide bridge and show that both EC-SOD dimers and EC-SOD monomers are present within the intracellular space. The proteolytic processing of the ECM-binding region in vitro was modulated by the redox status of Cys219, allowing cleavage under reducing conditions only. When wild-type EC-SOD or the monomeric variant Cys219Ser was expressed in mammalian cells proteolysis did not occur. However, when cells were exposed to oxidative stress conditions, proteolytic processing was observed for wild-type EC-SOD but not for the Cys219Ser variant. Although the cellular response to oxidative stress is complex, our data suggest that proteolytic removal of the ECM-binding region is regulated by the intracellular generation of an EC-SOD monomer and that Cys219 plays an important role as a redox switch allowing the cellular machinery to secrete cleaved EC-SOD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aorta
/
Superóxido Dismutase
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Estresse Oxidativo
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Subunidades Proteicas
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Cisteína
/
Proteólise
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article