Expression Of Selenium-binding Protein 1 Research Articles

Expression of selenium‐binding protein 1 characterizes intestinal cell maturation and predicts survival for patients with colorectal cancer

To identify candidate genes involved in the development of colorectal cancer, we used cDNA microarrays to analyze gene expression differences between human colorectal tumors and paired adjacent normal mucosa. We identified approximately 3.5-fold significant downregulation of selenium-binding protein 1 (SBP1) in colorectal tumors compared to normal mucosa (p = 0.003). Importantly, stage III colorectal cancer patients with low tumor-SBP1 expression had significantly shorter disease-free and overall survival as compared with those patients with high tumor-SBP1 expression (p = 0.04 and 0.03, respectively). We further characterized the role of SBP1 in colorectal cancer in vivo and in vitro. In normal tissue, SBP1 was maximally expressed in terminally differentiated epithelial cells on the luminal surface of crypts in the large intestine. Consistent with this in vivo localization, SBP1 was upregulated during in vitro colonic cell differentiation along the absorptive (Caco-2) and secretory (HT29 Clones 16E and 19A) cell lineages. Downregulation (approximately 50%) of SBP1 expression by small interfering RNA in colonic cancer cells was associated with reduced expression of another epithelial differentiation marker, carcinoembryonic antigen (CEA), although PCNA and p21(WAF1/cip1 )expression were not altered. These data demonstrate that higher expression of SBP1 is associated with differentiation of the normal colonic epithelia and may be a positive prognostic factor for survival in stage III colorectal carcinoma.

Relationship between the expression of heat shock protein 25 and selenium binding protein 1 with ischemia/reperfusion lung injury in vivo: experiment with rats

To analyze the differential expression proteins of rat ischemia/reperfusion (I/R) lung tissues in vivo and normal lung tissues by comparative proteome analysis, and to study the mechanism of donor lung I/R injury. Forty male SD rats were randomly divided into 2 equal groups: I/R group undergoing mimic orthotopic left lung auto-grafting and harvesting of the left lung five hours after the operation, and control group undergoing isolation of the left hilus of lung and then harvesting of the left lung. The differential proteins in the left ventricle of transplanted heart were separated by means of immobilized pH gradient-based two-dimensional gel electrophoresis (2-DE), identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), and searched through Matrix Science software system. Western blotting was used to verify part of the differentially expressed proteins. Well-resolved and reproducible 2-DE profile of rat I/R lung tissues and normal lung tissues were obtained. In the I/R lung tissue profile, the average spot number from 3 gels was 489 +/- 52 spots (P > 0.05) with an average matching rate of 89.28% (P > 0.05), and in the control group, the average spot number from 3 gels was 511 +/- 83 spots (P > 0.05) with an average matching rate of 91.22% (P > 0.05). Fourteen differential proteins were identified by peptide mass fingerprinting (PMF) searched in Matrix Science (P < 0.05). Western blotting confirmed that the protein expression of selenium binding protein 1 (SBP-1) and heat shock protein 25 (HSP25) increased at the early stage of I/R group. The protein expression of HSP25 and SBP-1 with stress protection function is upregulated in the early stage of lung I/R injury. Other differentially expressed proteins identified may have important functions in energy metabolism, tissue stress, cell apoptosis, and signal transduction.

Selenium-Binding Protein 1 expression in ovaries and ovarian tumors in the laying hen, a spontaneous model of human ovarian cancer

Objective. Reduced Selenium-Binding Protein 1 (SELENBP1) expression was recently shown in multiple cancers. There is little information on the expression and function of SELENBP1 in cancer progression. In order to develop a better understanding of the role of SELENBP1 in ovarian cancer, our objective was to determine if SELENBP1 is expressed in the normal ovaries and ovarian tumors in the egg-laying hen, a spontaneous model of human ovarian cancer. Methods. SPB1 mRNA expression in normal ovary ( n = 20) and ovarian tumors ( n = 23) was evaluated by RT-PCR. Relative levels of mRNA were compared by quantitative RT-PCR (qRT-PCR) in selected samples. SELENBP1 protein expression was evaluated by 1D Western blot and immunohistochemistry with a commercial anti-human SELENBP1 antibody. Results. SELENBP1 mRNA and protein was expressed in 100% of normal and ovarian tumors and qRT-PCR confirmed decreased mRNA expression in 80% of ovarian tumors. SELENBP1 was primarily localized in surface epithelial cells of normal ovaries. In ovaries containing early tumor lesions, SELENBP1 expression was reduced in the surface epithelium near the tumor and was expressed in tumor cells, while more distant regions with normal histology retained SELENBP1 expression in the surface epithelium. Conclusions. We have shown for the first time that SELENBP1 is expressed in both normal ovaries and ovarian tumors in the hen and that SELENBP1 expression is altered in the vicinity of the tumor. Furthermore, SELENBP1 expression in normal ovarian surface epithelium and in ovarian tumors parallels that previously reported for ovarian cancer in women .

An organic selenium compound attenuates apomorphine-induced stereotypy in mice

Selenium compounds display neuroprotective activities mediated at least in part by their antioxidant actions. Oxidative damage has been implicated in psychiatric disorders including schizophrenia and bipolar disorder, and an alteration in expression of selenium-binding protein-1 ( SELENBP-1) has been recently reported in both the blood and brain of schizophrenic patients. In the present study we examined the effects of the organic selenium compound 3′3-ditrifluoromethyldiphenyl diselenide [(F 3CPhSe) 2] on apomorphine-induced stereotypy in mice, an animal model of psychosis. Systemic administration of (F 3CPhSe) 2 at the highest dose used (25.0 μmol/kg in a 10.0 ml/kg injection volume) significantly reduced apomorphine-induced stereotyped behaviors. A series of control experiments showed that the same dose of (F 3CPhSe) 2 did not affect open-field behavior, habituation, or aversively motivated memory. The results indicate that organic selenium compounds should be further investigated as agents with possible antipsychotic properties.

Suppression of human selenium‐binding protein 1 is a late event in colorectal carcinogenesis and is associated with poor survival

The purpose of this study was to analyze altered protein expression in cancer tissues and determine its relationship to prognosis in colorectal carcinomas. We performed proteomic expression analysis on 14 colorectal carcinomas and matched nontumorous colonic mucosa by 2-DE and MALDI-TOF-MS. Comparative analysis of the respective spot patterns on 2-DE showed 14 spots that were markedly changed in the colorectal carcinomas. Among them, selenium-binding protein 1 (SELENBP1) was markedly decreased in 12 (85%) carcinomas. The reduced expression of SELENBP1 was further supported by Western blot analysis and immunohistochemistry. Suppression of SELENBP1 was further analyzed in another eight-paired adenomas and carcinomas from the same patients using Western blot analysis and immunohistochemistry, and revealed that one adenoma and seven carcinomas exhibited markedly reduced SELENBP1 expression. Patients with low levels of SELENBP1 expression had significantly lower overall survival rates (72 vs. 85%, p = 0.021) among the 240 stages II and III colorectal carcinomas by using tissue microarray analysis. Our findings indicate that suppression of SELENBP1 is a frequent and late event in colorectal carcinogenesis, and may contribute to the rapid progression of colorectal carcinoma.

Selenium-Binding Protein-1 in Smooth Muscle Cells is Downregulated in a Rhesus Monkey Model of Chronic Allograft Nephropathy

Treating patients with kidney failure by organ transplantation has been extraordinarily successful. Although, current immunosuppressants have improved short-term allograft survival, most transplants are eventually lost due to chronic allograft nephropathy (CAN). The molecular mechanisms underlying CAN are poorly understood. Smooth muscle cells (SMC) play a major role in the pathogenesis of CAN by contributing to the thickening of the intima and narrowing of the lumen of blood vessels. We show that selenium-binding protein-1 (SBP-1), a protein implicated in protein trafficking and secretion, is localized primarily to SMC in vivo. SBP-1 was heavily tyrosine-phosphorylated in vivo. Remarkably, SBP-1 was absent or strongly downregulated in vascular SMC in monkey kidney allografts with CAN. In contrast, the SMC alpha-actin was strongly expressed in the vascular SMC of the same allografts, indicating that the decrease in SBP-1 was not due to a global decrease in SMC proteins. Out of four growth factors implicated in the pathogenesis of CAN, only TGF-beta blocked the expression of SBP-1; thus, TGF-beta could regulate the expression of SBP-1 in CAN. These results show that SBP-1 localizes primarily to SMC in vivo and implicate this phosphoprotein in the effects of TGF-beta on SMC and in the process of CAN.

Reduced selenium-binding protein 1 expression is associated with poor outcome in lung adenocarcinomas.

The effects of selenium, an essential nutrient with anti-carcinogenic properties, are mediated by selenium-binding proteins. The protein expression status of human selenium-binding protein 1 (SBP1) in human tumours and the exact function of this protein are not known. In this study, quantitative two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was used on 93 lung adenocarcinomas and ten uninvolved lung samples. Two likely isoforms of a 56 kD protein that showed a significantly decreased abundance in lung adenocarcinomas were observed. Tandem mass spectrometry and 2-D western blot analysis identified these two proteins as human SBP1. Tumour tissue microarrays were utilized to examine the cellular expression patterns of SBP1 using immunohistochemistry. The same tissue samples were examined for SBP1 mRNA expression using oligonucleotide microarrays. Two major SBP1 isoforms were detected, with an acidic isoform (457) being significantly down-regulated in lung adenocarcinomas compared with normal lung (p = 0.02). Two additional more acidic SBP1 isoforms were only observed in normal lung. SBP1 protein isoforms and SBP1 mRNA levels were significantly decreased in poorly differentiated (versus moderately and well-differentiated), T2-T4 (versus T1), and bronchus-derived (versus bronchioloalveolar) tumours. Low levels of SBP1 protein (native form, 460) correlated significantly with poor survival (p = 0.007). The lack of SBP1 expression was not due to gene deletion. Treatment of A549 lung adenocarcinoma cells with the methylation inhibitor 5-azacytidine did not affect expression of the SBP1 protein. Analysis of the tumour proliferation status using Ki-67 suggests that down-regulated expression of SBP1 may reflect increased cell proliferation and decreased differentiation in lung adenocarcinomas.

Enhancement of Acetaminophen Cytotoxicity in Selenium-binding Protein-overexpressed COS-1 Cells

The role of selenium-binding protein (SeBP), which has a high ability to associate with acetaminophen (AAP), on the cytotoxicity of AAP was studied. To clarify this issue, we examined the cytotoxic effect of AAP using COS cells stably expressing SeBP. Expression of SeBP enhanced the susceptibility of the cells to AAP-induced cytotoxicity. Several clones of SeBP-expressed COS cells were obtained, and they exhibited different degrees of susceptibility toward AAP. It was found that there is an inverse correlation between the expression level and the cell viability (r=-0.872). On the other hand, no increase in toxicity was observed in the SeBP-expressed cells treated with N-acetyl-p-quinone imine (NAPQI), which is an active metabolite of AAP. These results show that SeBP is an important factor in AAP hepatotoxicity. Moreover, our data suggest that the toxic mechanism of AAP differs from that of NAPQI.