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Cell Mol Life Sci. 2017 Feb;74(4):607-616. doi: 10.1007/s00018-016-2339-2. Epub 2016 Aug 25.

Selenoproteins and oxidative stress-induced inflammatory tumorigenesis in the gut.

Author information

1
Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
2
Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical School, 1065D Medical Research Building IV, B-2215 Garland Avenue, Nashville, TN, 37232, USA.
3
Department of Cancer Biology, Vanderbilt University Medical School, Nashville, USA.
4
Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical School, 1065D Medical Research Building IV, B-2215 Garland Avenue, Nashville, TN, 37232, USA. Christopher.williams@vanderbilt.edu.
5
Department of Cancer Biology, Vanderbilt University Medical School, Nashville, USA. Christopher.williams@vanderbilt.edu.
6
Vanderbilt Ingram Cancer Center, Vanderbilt University Medical School, Nashville, USA. Christopher.williams@vanderbilt.edu.
7
Veterans Affairs Tennessee Valley HealthCare System, Nashville, TN, USA. Christopher.williams@vanderbilt.edu.

Abstract

Selenium is an essential micronutrient that is incorporated into at least 25 selenoproteins encoded by the human genome, many of which serve antioxidant functions. Because patients with inflammatory bowel disease (IBD) demonstrate nutritional deficiencies and are at increased risk for colon cancer due to heightened inflammation and oxidative stress, selenoprotein dysfunction may contribute to disease progression. Over the years, numerous studies have analyzed the effects of selenoprotein loss and shown that they are important mediators of intestinal inflammation and carcinogenesis. In particular, recent work has focused on the role of selenoprotein P (SEPP1), a major selenium transport protein which also has endogenous antioxidant function. These experiments determined SEPP1 loss altered immune and epithelial cellular function in a murine model of colitis-associated carcinoma. Here, we discuss the current knowledge of SEPP1 and selenoprotein function in the setting of IBD, colitis, and inflammatory tumorigenesis.

KEYWORDS:

Antioxidant; Enteroids; Glutathione peroxidase; Inflammation; Interferon-γ; Selenoprotein P; Stem cells

PMID:
27563706
PMCID:
PMC5274549
DOI:
10.1007/s00018-016-2339-2
[Indexed for MEDLINE]
Free PMC Article

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