Aberrant expression of selenoproteins in the progression of colorectal cancer

Murawaki, Yoshiyuki; Tsuchiya, Hiroyuki; Kanbe, Takamasa; Harada, Kiyoshi; Yashima, Kazuo; Nozaka, Kimiyasu; Tanida, Osamu; Kohno, Masanori; Mukoyama, Tomoyuki; Nishimuki, Eiji; Kojo, Haruhiko; Matsura, Tatsuya; Takahashi, Kazuhiko; Osaki, Mitsuhiko; Ito, Hisao; Yodoi, Junji; Murawaki, Yoshikazu; Shiota, Goshi

doi:10.1016/j.canlet.2007.10.019

Cited by 115 publications

(90 citation statements)

References 34 publications

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“…283 GPx2 is upregulated in some types of cancer, particularly of gastrointestinal origin. 284 A recent study has shown that lower expression of GPx2 increases migration and invasion of cancer cell clones, but decreases their growth, thus depending on the stage of tumour development. 285 Finally, TrxR1 is probably the most investigated Se-protein in its relationship to cancer.…”

Section: Male Infertilitymentioning

confidence: 99%

Selenium biochemistry and its role for human health

Roman¹,

Jitaru²,

Barbante³

2014

Metallomics

652

451

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Despite its very low level in humans, selenium plays an important and unique role among the (semi)metal trace essential elements because it is the only one for which incorporation into proteins is genetically encoded, as the constitutive part of the 21st amino acid, selenocysteine. Twenty-five selenoproteins have been identified so far in the human proteome. The biological functions of some of them are still unknown, whereas for others there is evidence for a role in antioxidant defence, redox state regulation and a wide variety of specific metabolic pathways. In relation to these functions, the selenoproteins emerged in recent years as possible biomarkers of several diseases such as diabetes and several forms of cancer. Comprehension of the selenium biochemical pathways under normal physiological conditions is therefore an important requisite to elucidate its preventing/therapeutic effect for human diseases. This review summarizes the most recent findings on the biochemistry of active selenium species in humans, and addresses the latest evidence on the link between selenium intake, selenoproteins functionality and beneficial health effects. Primary emphasis is given to the interpretation of biochemical mechanisms rather than epidemiological/observational data. In this context, the review includes the following sections: (1) brief introduction; (2) general nutritional aspects of selenium; (3) global view of selenium metabolic routes; (4) detailed characterization of all human selenoproteins; (5) detailed discussion of the relation between selenoproteins and a variety of human diseases.

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Section: Male Infertilitymentioning

confidence: 99%

Selenium biochemistry and its role for human health

Roman¹,

Jitaru²,

Barbante³

2014

Metallomics

652

451

View full text Add to dashboard Cite

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“…High Se supplementation (2 lg/g body weight) was shown to prevent inflammation and improve the health of affected tissue in a rat model of dextran sodium sulfate (DSS)-induced colitis (249). Selp is among the selenoproteins expressed at the highest levels in the intestine (104,179), and this protein may play a particularly important role in the pathogenesis of colitis. In a mouse model of colitis utilizing DSS treatment, Selp mRNA was decreased in the colon of DSS-treated mice (237).…”

Section: Intestinal Inflammation and Food-borne Illnessesmentioning

confidence: 99%

The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities

Huang

Rose

Hoffmann

2012

Antioxidants & Redox Signaling

710

496

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Dietary selenium (]Se), mainly through its incorporation into selenoproteins, plays an important role in inflammation and immunity. Adequate levels of Se are important for initiating immunity, but they are also involved in regulating excessive immune responses and chronic inflammation. Evidence has emerged regarding roles for individual selenoproteins in regulating inflammation and immunity, and this has provided important insight into mechanisms by which Se influences these processes. Se deficiency has long been recognized to negatively impact immune cells during activation, differentiation, and proliferation. This is related to increased oxidative stress, but additional functions such as protein folding and calcium flux may also be impaired in immune cells under Se deficient conditions. Supplementing diets with above-adequate levels of Se can also impinge on immune cell function, with some types of inflammation and immunity particularly affected and sexually dimorphic effects of Se levels in some cases. In this comprehensivearticle, the roles of Se and individual selenoproteins in regulating immune cell signaling and function are discussed. Particular emphasis is given to how Se and selenoproteins are linked to redox signaling, oxidative burst, calcium flux, and the subsequent effector functions of immune cells. Data obtained from cell culture and animal models are reviewed and compared with those involving human physiology and pathophysiology, including the effects of Se levels on inflammatory or immune-related diseases including anti-viral immunity, autoimmunity, sepsis, allergic asthma, and chronic inflammatory disorders. Finally, the benefits and potential adverse effects of intervention with Se supplementation for various inflammatory or immune disorders are discussed. Antioxid. Redox Signal. 16, 705-743.

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“…4). The different regulation of the glutathione peroxidase isoenzymes is intriguing with regard to the opposite distribution of GPx1 and GPx2 along the crypt to villus axis in the intestine and their reciprocal expression pattern in tumorous versus nontumorous human colon tissue, as reported by others (10,12,44).…”

Section: Differentiation Triggers An Increase In Gpx4 Protein Expressmentioning

confidence: 75%

Induction of Glutathione Peroxidase 4 Expression during Enterocytic Cell Differentiation

Speckmann¹,

Bidmon²,

Pinto³

et al. 2011

Journal of Biological Chemistry

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Glutathione peroxidase 4 (GPx4), an abundant selenoenzyme, is ubiquitously expressed in a tissue-, cell-and differentiationdependent manner, and it is localized in cytoplasmic, mitochondrial, and nuclear cellular compartments. Here, we report cytoplasmic and nuclear localization of GPx4 in Caco-2 intestinal epithelial cells. Enterocytic differentiation of Caco-2 cells triggers an increase in GPx4 mRNA and protein levels, mediated by enhanced promoter activity. We identified a combined cAMP response element (CREB) and CCAAT/enhancer binding protein (C/EBP) site as critical for the differentiation-triggered GPx4 promoter activity. Induction of GPx4 correlated with C/EBP␣ transcript levels during differentiation, suggesting a role of C/EBP␣ as regulator of enterocytic GPx4 expression. Consistent with the in vitro results, GPx4 protein was detected in cytoplasmic and nuclear compartments of enterocytes in human intestinal epithelia. GPx4 is uniformly expressed in colonic crypts and is differentially expressed along the cryptto-villus axis in the small intestine with a more pronounced expression of GPx4 in the upper villi, which contain fully differentiated enterocytes. These data suggest that intestinal GPx4 expression is modulated by the enterocytic differentiation program, and the results support a direct role of nuclear GPx4 in the (selenium-dependent) prevention of oxidative damage in the gastrointestinal tract.The essential trace element selenium is of fundamental importance to human health, acting through low molecular weight selenium compounds as well as selenocysteine-containing selenoproteins (1). Adequate selenium intake, maintaining optimized expression and/or activity of selenoproteins, has been proposed to be beneficial with respect to prevention of several oxidative stress-related neurodegenerative and cardiovascular diseases and, most notably, cancer (1, 2). Secondary end point analyses of the Nutritional Prevention of Cancer study provided compelling evidence that dietary supplementation with 200 g selenium/day in form of high selenium yeast lowered the incidence of lung, prostate, and colorectal cancer as well as cancer mortality (3). Since the publication of this landmark trial, the anticarcinogenic capacity of selenium compounds has been further substantiated, particularly with regard to the gastrointestinal tract (4 -7). Mice with genetically impaired biosynthesis of selenoproteins due to a mutant selenocysteine transfer RNA gene have been shown to be more susceptible to colon cancer than wild-type mice, thus suggesting a key role for selenoproteins as mediators of the cancer-protective effects of selenium in the colon (5). Selenoproteins that are abundantly expressed in the healthy gastrointestinal tract and putatively relevant in malignant transformation comprise thioredoxin reductases, selenoprotein P, and glutathione peroxidases (GPx) 3 (8 -11). To date, five selenium-dependent GPx isoenzymes have been identified in humans: GPx1 and GPx2 are highly expressed in the intestinal epithelium, havi...

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Aberrant expression of selenoproteins in the progression of colorectal cancer

Cited by 115 publications

References 34 publications

Selenium biochemistry and its role for human health

Selenium biochemistry and its role for human health

The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities

Induction of Glutathione Peroxidase 4 Expression during Enterocytic Cell Differentiation

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