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Selenoproteins and oxidative stress-induced inflammatory tumorigenesis in the gut

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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.

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Abbreviations

SEPP1:

Selenoprotein P

CAC:

Colitis-associated cancer

IBD:

Inflammatory bowel disease

CD:

Crohn’s disease

UC:

Ulcerative colitis

SeP:

Selenoprotein

GPx:

Glutathione Peroxidase

ROS:

Reactive oxygen species

Se:

Selenium

CRC:

Colorectal cancer

AOM:

Azoxymethane

DSS:

Dextran sulfate sodium

Sec:

Selenocysteine

Cys:

Cysteine

GSH:

Glutathione

ACF:

Aberrant crypt foci

TNBS:

2,4,6-Trinitrobenzene sulphonic acid

IFN-γ:

Interferon-γ

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Authors and Affiliations

  1. 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

    Sarah P. Short & Christopher S. Williams

  2. Department of Cancer Biology, Vanderbilt University Medical School, Nashville, USA

    Sarah P. Short & Christopher S. Williams

  3. Vanderbilt Ingram Cancer Center, Vanderbilt University Medical School, Nashville, USA

    Christopher S. Williams

  4. Veterans Affairs Tennessee Valley HealthCare System, Nashville, TN, USA

    Christopher S. Williams

  5. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA

    Caitlyn W. Barrett

Authors
  1. Caitlyn W. Barrett
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  2. Sarah P. Short
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  3. Christopher S. Williams
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Correspondence to Christopher S. Williams.

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Barrett, C.W., Short, S.P. & Williams, C.S. Selenoproteins and oxidative stress-induced inflammatory tumorigenesis in the gut. Cell. Mol. Life Sci. 74, 607–616 (2017). https://doi.org/10.1007/s00018-016-2339-2

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  • DOI: https://doi.org/10.1007/s00018-016-2339-2

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