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Media type:
E-Article
Title:
Physiological functions of GPx2 and its role in inflammation‐triggered carcinogenesis
Contributor:
Brigelius‐Flohé, Regina;
Kipp, Anna Patricia
Published:
Wiley, 2012
Published in:
Annals of the New York Academy of Sciences, 1259 (2012) 1, Seite 19-25
Language:
English
DOI:
10.1111/j.1749-6632.2012.06574.x
ISSN:
0077-8923;
1749-6632
Origination:
Footnote:
Description:
Mammalian glutathione peroxidases (GPxs) are reviewed with emphasis on the role of the gastrointestinal GPx2 in tumorigenesis. GPx2 ranks high in the hierarchy of selenoproteins, corroborating its importance. Colocalization of GPx2 with the Wnt pathway in crypt bases of the intestine and its induction by Wnt signals point to a role in mucosal homeostasis, but GPx2 might also support tumor growth when increased by a dysregulated Wnt pathway. In contrast, the induction of GPx2 by Nrf2 activators and the upregulation of COX2 in cells with a GPx2 knockdown reveal inhibition of inflammation and suggest prevention of inflammation‐mediated carcinogenesis. The Janus‐faced role of GPx2 has been confirmed in a mouse model of inflammation‐associated colon carcinogenesis (AOM/DSS), where GPx2 deletion increased inflammation and consequently tumor development, but decreased tumor size. The model further revealed a GPx2‐independent decrease in tumor development by selenium (Se) and detrimental effects of the Nrf2‐activator sulforaphane in moderate Se deficiency.