Selenoproteins and oxidative stress-induced inflammatory tumorigenesis in the gut

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.

Single-Cell Analysis Reveals Regional Reprogramming during Adaptation to Massive Small Bowel Resection in Mice

“…SEPP1 is a secreted glycoprotein with important immunomodulatory and antioxidant effects in the intestine [24][25][26] . Representative immunohistochemistry images of SEPP1 show qualitative changes consistent with our scRNA-seq analysis (Figure 5b).…”

“…Quantification of this immunostaining via immunofluorescence demonstrated significant increases in SEPP1 (1.4 fold relative fluorescent intensity, p<0.05) in SBR relative to sham (Figure 5c). Furthermore, SEPP1 has been shown to suppress inflammation-associated tumorigenesis, in part through its effects on macrophage polarization, more specifically, by suppressing M2 associated Ym1 expression 25,27 . Interestingly, this is consistent with RNA-sequencing analysis we performed on sub-epithelial tissue from sham and SBR mice, showing that Ym1 is the second most depleted transcript in SBR mice (-6.19 fold depleted, p <0.05, unpublished).…”

Bacterial DNA induces the formation of heat-resistant disease-associated “Tetz-proteins” in human plasma

“…We believe that a larger cohort may provide more statistically significant findings. Notably, CD5L, EIF5A1, FINC, and SEPP1 particularly attracted our attention as, according to the literature, they are associated with tumorigenesis [51, 83-85]. In the present study, heat-resistant fractions of these proteins were identified in pancreatic cancer plasma, but not in normal plasma, and formed only after eDNA treatment, suggesting a role of this conversion in tumorigenesis.…”

Effect of Cardioxane and Selenium on Lipoperoxidation and Levels of Dopamine in Rat Brain and Heart

“…Calcium-magnesium-dependent ATPase activity decreased in the heart and cortex regions of the animals that received selenium alone or combined, probably as a consequence of the changes in the enzyme affinity [27]. This effect may probably be because cellular calcium signaling is subjected to thiol-redox regulation by the selenoproteins [28] [29]. These results could be related with the reports of Naziroglu et al [30], who suggested that selenium increases the activity of Ca 2+ -ATPase thus, producing protective effect on the substances that increase brain lesions, by the inhibition of free radical production and regulation of calcium-dependent processes, as well as supporting the redox antioxidant system.…”