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Wancai Yang - One of the best experts on this subject based on the ideXlab platform.
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RESEARCH ARTICLE Quantitative Proteomic Analysis Reveals That Anti-Cancer Effects of Selenium-Binding Protein 1 In Vivo Are Associated with Metabolic Pathways
2016Co-Authors: Qi Ying, Alan M. Diamond, Emmanuel Ansong, Wancai YangAbstract:Previous studies have shown the tumor-suppressive role of Selenium-Binding Protein 1 (SBP1), but the underlying mechanisms are unclear. In this study, we found that induction of SBP1 showed significant inhibition of colorectal cancer cell growth and metastasis in mice. We further employed isobaric tags for relative and absolute quantitation (iTRAQ) to identify Proteins that were involved in SBP1-mediated anti-cancer effects in tumor tissues. We identified 132 differentially expressed Proteins, among them, 53 Proteins were upregu-lated and 79 Proteins were downregulated. Importantly, many of the differentially altered Proteins were associated with lipid/glucose metabolism, which were also linked to Glycoly-sis, MAPK, Wnt, NF-kB, NOTCH and epithelial-mesenchymal transition (EMT) signaling pathways. These results have revealed a novel mechanism that SBP1-mediated cancer in-hibition is through altering lipid/glucose metabolic signaling pathways
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Abstract 1197: Selenium-Binding Protein 1-mediated tumor suppression is associated with alterations of lipid/glucose metabolic pathways in vivo
Molecular and Cellular Biology, 2015Co-Authors: Qi Ying, Alan M. Diamond, Emmanuel Ansong, Xiaomei Bie, Wancai YangAbstract:Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Selenium-Binding Protein 1 (SBP1) is significantly decreased in most of human cancers including liver, prostate, breast, lung and colorectal cancers, and the decreased SBP1 is associated with poor clinical outcomes and recurrence, showing a tumor suppressor role. However, the underlying mechanisms are still unclear. In this study, we constructed a doxycycline inducible SBP1 plasmid (pRetroX-Tight- Pur-SBP1) and established a stable colorectal cancer cell line HCT116-TetSBP1, then injected the HCT116-TetSBP1 cell line into BALB/c CD-1 Nu female mice subcutaneously on the right flank, the control cell line HCT116-Act was injected in the left flank. The mice was supplied with Doxycycline (200 μg/mL) in drinking water. Four weeks after injection, the tumors from both sides were isolated and the weight (gm) and volume (mm3) of tumors were determined. Tumors were stored at -80°C until used for immunoblot and isobaric tags for relative and absolute quantitation (iTRAQ) analysis. We found that induction of SBP1 showed significant inhibition of cancer cell growth and metastasis in mice. iTRAQ analysis showed 132 differentially expressed Proteins in response to SBP1 induction, among them, 53 Proteins were upregulated and 79 Proteins were downregulated. Importantly, many of the differentially altered Proteins were associated with lipid/glucose metabolism. Although all seven Proteins related to glucose metabolism (GAA, GAPDH, ALDH2, Thioredoxin, ENO3, UGDH and Lumican) were downregulated by SBP1 induction, thirteen lipid metabolism-related Proteins act differentially on SBP1-medited signal transduction (five Proteins were upregulated: DKK1, HSP60, DHCR7, ANXA4 and AGPAT5, and eight Proteins were downregulated: LPCAT2, GPX5, GAPDH, NME2, ALDH2, BPIFA3, PPIA and FABP4). Bioinformatic analysis showed that these Proteins were involved in Glycolysis, MAPK, Wnt, NF-kB, NOTCH and epithelial-mesenchymal transition (EMT) signaling pathways. Taken together, our results have revealed a novel mechanism that SBP1-mediated cancer inhibition is through altering lipid/glucose metabolic signaling pathways. Note: This abstract was not presented at the meeting. Citation Format: Qi Ying, Emmanuel Ansong, Alan M. Diamond, Zhaoxin Lu, Xiaomei Bie, Wancai Yang. Selenium-Binding Protein 1-mediated tumor suppression is associated with alterations of lipid/glucose metabolic pathways in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1197. doi:10.1158/1538-7445.AM2015-1197
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abstract 1197 Selenium Binding Protein 1 mediated tumor suppression is associated with alterations of lipid glucose metabolic pathways in vivo
Cancer Research, 2015Co-Authors: Qi Ying, Alan M. Diamond, Emmanuel Ansong, Xiaomei Bie, Wancai YangAbstract:Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Selenium-Binding Protein 1 (SBP1) is significantly decreased in most of human cancers including liver, prostate, breast, lung and colorectal cancers, and the decreased SBP1 is associated with poor clinical outcomes and recurrence, showing a tumor suppressor role. However, the underlying mechanisms are still unclear. In this study, we constructed a doxycycline inducible SBP1 plasmid (pRetroX-Tight- Pur-SBP1) and established a stable colorectal cancer cell line HCT116-TetSBP1, then injected the HCT116-TetSBP1 cell line into BALB/c CD-1 Nu female mice subcutaneously on the right flank, the control cell line HCT116-Act was injected in the left flank. The mice was supplied with Doxycycline (200 μg/mL) in drinking water. Four weeks after injection, the tumors from both sides were isolated and the weight (gm) and volume (mm3) of tumors were determined. Tumors were stored at -80°C until used for immunoblot and isobaric tags for relative and absolute quantitation (iTRAQ) analysis. We found that induction of SBP1 showed significant inhibition of cancer cell growth and metastasis in mice. iTRAQ analysis showed 132 differentially expressed Proteins in response to SBP1 induction, among them, 53 Proteins were upregulated and 79 Proteins were downregulated. Importantly, many of the differentially altered Proteins were associated with lipid/glucose metabolism. Although all seven Proteins related to glucose metabolism (GAA, GAPDH, ALDH2, Thioredoxin, ENO3, UGDH and Lumican) were downregulated by SBP1 induction, thirteen lipid metabolism-related Proteins act differentially on SBP1-medited signal transduction (five Proteins were upregulated: DKK1, HSP60, DHCR7, ANXA4 and AGPAT5, and eight Proteins were downregulated: LPCAT2, GPX5, GAPDH, NME2, ALDH2, BPIFA3, PPIA and FABP4). Bioinformatic analysis showed that these Proteins were involved in Glycolysis, MAPK, Wnt, NF-kB, NOTCH and epithelial-mesenchymal transition (EMT) signaling pathways. Taken together, our results have revealed a novel mechanism that SBP1-mediated cancer inhibition is through altering lipid/glucose metabolic signaling pathways. Note: This abstract was not presented at the meeting. Citation Format: Qi Ying, Emmanuel Ansong, Alan M. Diamond, Zhaoxin Lu, Xiaomei Bie, Wancai Yang. Selenium-Binding Protein 1-mediated tumor suppression is associated with alterations of lipid/glucose metabolic pathways in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1197. doi:10.1158/1538-7445.AM2015-1197
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Evidence That Selenium Binding Protein 1 Is a Tumor Suppressor in Prostate Cancer
PloS one, 2015Co-Authors: Emmanuel Ansong, Wancai Yang, Qi Ying, Dede N. Ekoue, Ryan Deaton, Andrew R. Hall, Andre Kajdacsy-balla, Peter H. Gann, Alan M. DiamondAbstract:Selenium-Binding Protein 1 (SBP1, SELENBP1, hSP56) is a Selenium-associated Protein shown to be at lower levels in tumors, and its lower levels are frequently predictive of a poor clinical outcome. Distinguishing indolent from aggressive prostate cancer is a major challenge in disease management. Associations between SBP1 levels, tumor grade, and disease recurrence following prostatectomy were investigated by duplex immunofluorescence imaging using a tissue microarray containing tissue from 202 prostate cancer patients who experienced biochemical (PSA) recurrence after prostatectomy and 202 matched control patients whose cancer did not recur. Samples were matched by age, ethnicity, pathological stage and Gleason grade, and images were quantified using the Vectra multispectral imaging system. Fluorescent labels were targeted for SBP1 and cytokeratins 8/18 to restrict scoring to tumor cells, and cell-by-cell quantification of SBP1 in the nucleus and cytoplasm was performed. Nuclear SBP1 levels and the nuclear to cytoplasm ratio were inversely associated with tumor grade using linear regression analysis. Following classification of samples into quartiles based on the SBP1 levels among controls, tumors in the lowest quartile were more than twice as likely to recur compared to those in any other quartile. Inducible ectopic SBP1 expression reduced the ability of HCT-116 human tumor cells to grow in soft agar, a measure of transformation, without affecting proliferation. Cells expressing SBP1 also demonstrated a robust induction in the phosphorylation of the p53 tumor suppressor at serine 15. These data indicate that loss of SBP1 may play an independent contributing role in prostate cancer progression and its levels might be useful in distinguishing indolent from aggressive disease.
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Quantitative Proteomic Analysis Reveals That Anti-Cancer Effects of Selenium-Binding Protein 1 In Vivo Are Associated with Metabolic Pathways
PloS one, 2015Co-Authors: Qi Ying, Wancai Yang, Alan M. Diamond, Emmanuel Ansong, Xiaomei BieAbstract:Previous studies have shown the tumor-suppressive role of Selenium-Binding Protein 1 (SBP1), but the underlying mechanisms are unclear. In this study, we found that induction of SBP1 showed significant inhibition of colorectal cancer cell growth and metastasis in mice. We further employed isobaric tags for relative and absolute quantitation (iTRAQ) to identify Proteins that were involved in SBP1-mediated anti-cancer effects in tumor tissues. We identified 132 differentially expressed Proteins, among them, 53 Proteins were upregulated and 79 Proteins were downregulated. Importantly, many of the differentially altered Proteins were associated with lipid/glucose metabolism, which were also linked to Glycolysis, MAPK, Wnt, NF-kB, NOTCH and epithelial-mesenchymal transition (EMT) signaling pathways. These results have revealed a novel mechanism that SBP1-mediated cancer inhibition is through altering lipid/glucose metabolic signaling pathways.
Thressa C. Stadtman - One of the best experts on this subject based on the ideXlab platform.
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Solution NMR Structure of Selenium-Binding Protein from Methanococcus vannielii
The Journal of biological chemistry, 2008Co-Authors: Motoshi Suzuki, Duck-yeon Lee, Nwakaego Inyamah, Thressa C. Stadtman, Nico TjandraAbstract:Selenium is an important nutrient. The lack of Selenium will suppress expression of various enzymes that will lead to cell abnormality and diseases. However, high concentrations of free Selenium are toxic to the cell because it adversely affects numerous cell metabolic pathways. In Methanococcus vannielii, Selenium transport in the cell is established by the Selenium-Binding Protein, SeBP. SeBP sequesters Selenium during transport, thus regulating the level of free Selenium in the cell, and delivers it specifically to the selenophosphate synthase enzyme. In solution, SeBP is an oligomer of 8.8-kDa subunits. It is a symmetric pentamer. The solution structure of SeBP was determined by NMR spectroscopy. Each subunit of SeBP is composed of an alpha-helix on top of a 4-stranded twisted beta-sheet. The stability of the five subunits stems mainly from hydrophobic interactions and supplemented by hydrogen bond interactions. The loop containing Cys(59) has been shown to be important for Selenium Binding, is flexible, and adopts multiple conformations. However, the cysteine accessibility is restricted in the structure, reducing the possibility of the Binding of free Selenium readily. Therefore, a different Selenium precursor or other factors might be needed to facilitate opening of this loop to expose Cys(59) for Selenium Binding.
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methanococcus vannielii Selenium Binding Protein sebp chemical reactivity of recombinant sebp produced in escherichia coli
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Kemberly G Patteson, Neel Trivedi, Thressa C. StadtmanAbstract:A Selenium-Binding Protein (SeBP) from Methanococcus vannielii was recently identified, and its gene was isolated and overexpressed in Escherichia coli [Self, W. T., Pierce, R. & Stadtman, T. C. (2004) IUBMB Life 56, 501–507]. SeBP and recombinant SeBP (rSeBP) migrated as ≈42-kDa species on native gels and as ≈33-kDa species on SDS gels. rSeBP consists of identical 8.8-kDa subunits, each containing a single cysteine residue. rSeBP isolated in the absence of reducing agents contained oxidized cysteine (89%) and very little bound Selenium (0.05 eq or less per subunit). Complete reduction of the oxidized cysteine residues in rSeBP with Tris(2-carboxyethyl)phosphine required addition of a denaturant, such as 1 M guanidine-hydrochloride. With selenite as the Selenium source and the isolated reduced Protein as sole reductant, Binding of one Selenium per tetramer under anaerobic conditions required four cysteine thiol groups, one on each subunit. In the corresponding reaction, with reduced glutathione (GSH), equimolar amounts of selenodiglutathione (GSSeSG) and glutathione disulfide are formed from selenite and 4 GSH. At GSH-to-selenite ratios >4:1, conversion of GSSeSG to a perselenide derivative, GSSe–, occurs. However, with the reduced rSeBP as sole electron donor in the reaction with selenite, further conversion of the R-SSeS-R product apparently did not occur. Prior alkylation of the cysteine thiol groups in reduced rSeBP prevented selenite reduction and Selenium Binding under comparable conditions.
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Cloning and Heterologous Expression of a Methanococcus vannielii Gene Encoding a Selenium‐Binding Protein
IUBMB life, 2004Co-Authors: William T. Self, Renee Pierce, Thressa C. StadtmanAbstract:The activation and incorporation of Selenium into selenocysteine containing selenoProteins has been well established in an Escherichia coli model system but there is little specific information concerning the transport and intracellular trafficking of Selenium in biological systems in general. A Selenium transport role is a possible function of a novel 42 kDa Selenium-Binding Protein that recently was purified from Methanococcus vannielii. The gene encoding a monomer of this Protein (Sbp) has been cloned, sequenced and heterologously expressed in E. coli. The 8.8 kDa gene product contains 81 amino acids. The recombinant Sbp (rSbp) Protein was shown to bind Selenium from added selenite. The bound Selenium appeared predominantly in dimeric and tetrameric forms of the Protein. The gene encoding Sbp occurs in an operon that contains a carbonic anhydrase gene and selenocysteine-containing formate dehydrogenase genes, suggesting possible roles in Selenium-dependent formate metabolism.
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cloning and heterologous expression of a methanococcus vannielii gene encoding a Selenium Binding Protein
Iubmb Life, 2004Co-Authors: William T. Self, Renee Pierce, Thressa C. StadtmanAbstract:The activation and incorporation of Selenium into selenocysteine containing selenoProteins has been well established in an Escherichia coli model system but there is little specific information concerning the transport and intracellular trafficking of Selenium in biological systems in general. A Selenium transport role is a possible function of a novel 42 kDa Selenium-Binding Protein that recently was purified from Methanococcus vannielii. The gene encoding a monomer of this Protein (Sbp) has been cloned, sequenced and heterologously expressed in E. coli. The 8.8 kDa gene product contains 81 amino acids. The recombinant Sbp (rSbp) Protein was shown to bind Selenium from added selenite. The bound Selenium appeared predominantly in dimeric and tetrameric forms of the Protein. The gene encoding Sbp occurs in an operon that contains a carbonic anhydrase gene and selenocysteine-containing formate dehydrogenase genes, suggesting possible roles in Selenium-dependent formate metabolism.
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Methanococcus vannielii Selenium metabolism: Purification and N-terminal amino acid sequences of a novel Selenium-Binding Protein and selenocysteine lyase
IUBMB life, 2004Co-Authors: Thressa C. StadtmanAbstract:Selenium is an essential component of several enzymes and Proteins in a number of methane-producing archae. Information concerning accessory Proteins that function in Selenium transport processes, however, is limited. A novel Selenium-Binding Protein with a potential transport role and a selenocysteine lyase that serves as a Selenium delivery Protein are present in Methanococcus vannielii. The Selenium-Binding Protein was purified from extracts of 75Se-labeled cells. Although there was gradual loss of 75Se during purification, the isolated Protein still could be detected as a radioactive 42 kDa species on native PAGE gels and as a 33 kDa species on SDS PAGE gels. The N-terminal amino acid sequence of residues 1 - 63 of the Protein was determined by automated Edman degradative analysis. The only homologous sequence detected in the recorded data base was that of a gene encoding an unknown Protein located in the genomic sequence of Methanococcus maripaludis. Cloning and expression of the corresponding gene from M. vannielii are described in a manuscript in press (Self et al.). A 47 kDa selenocysteine lyase isolated from M. vannielii extracts exhibited sequence homology to the NIFS family of Proteins that transport sulfur. The purified selenocysteine lyase catalyzed the elimination of an elemental form of Selenium from free selenocysteine and delivered this Selenium directly to selenophosphate synthetase. The synthetase converted the Selenium to selenophosphate in an ATP-dependent reaction.
Alan M. Diamond - One of the best experts on this subject based on the ideXlab platform.
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Selenium Binding Protein 1 alters energy metabolism in prostate cancer cells
The Prostate, 2020Co-Authors: Mostafa Elhodaky, Lenny Hong, Shrinidhi Kadkol, Alan M. DiamondAbstract:OBJECTIVE The broad goal of the research described in this study was to investigate the contributions of Selenium-Binding Protein 1 (SBP1) loss in prostate cancer development and outcome. METHODS SBP1 levels were altered in prostate cancer cell lines and the consequences on oxygen consumption, expression of Proteins associated with energy metabolism, and cellular transformation and migration were investigated. The effects of exposing cells to the SBP1 reaction products, H2 O2 and H2 S were also assessed. In silico analyses identified potential HNF4α Binding sites within the SBP1 promoter region and this was investigated using an inhibitor specific for that transcription factor. RESULTS Using in silico analyses, it was determined that the promoter region of SBP1 contains putative Binding sites for the HNF4α transcription factor. The potential for HNF4α to regulate SBP1 expression was supported by data indicating that HNF4α inhibition resulted in a dose-response increase in the levels of SBP1 messenger RNA and Protein, identifying HNF4α as a novel negative regulator of SBP1 expression in prostate cancer cells. The consequences of altering the levels of SBP1 were investigated by ectopically expressing SBP1 in PC-3 prostate cancer cells, where SBP1 expression attenuated anchorage-independent cellular growth and migration in culture, both properties associated with transformation. SBP1 overexpression reduced oxygen consumption in these cells and increased the activation of AMP-activated Protein kinase (AMPK), a major regulator of energy homeostasis. In addition, the reaction products of SBP1, H2 O2 , and H2 S also activated AMPK. CONCLUSIONS Based on the obtained data, it is hypothesized that SBP1 negatively regulates oxidative phosphorylation (OXPHOS) in the healthy prostate cells by the production of H2 O2 and H2 S and consequential activation of AMPK. The reduction of SBP1 levels in prostate cancer can occur due to increased Binding of HNF4α, acting as a transcriptional inhibitor to the SBP1 promoter. Consequently, there is a reduction in H2 O2 and H2 S-mediated signaling, inhibition of AMPK, and stimulation of OXPHOS and building blocks of biomolecules needed for tumor growth and progression. Other effects of SBP1 loss in tumor cells remain to be discovered.
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Selenium‐Binding Protein 1 alters energy metabolism in prostate cancer cells
The Prostate, 2020Co-Authors: Mostafa Elhodaky, Lenny Hong, Shrinidhi Kadkol, Alan M. DiamondAbstract:OBJECTIVE The broad goal of the research described in this study was to investigate the contributions of Selenium-Binding Protein 1 (SBP1) loss in prostate cancer development and outcome. METHODS SBP1 levels were altered in prostate cancer cell lines and the consequences on oxygen consumption, expression of Proteins associated with energy metabolism, and cellular transformation and migration were investigated. The effects of exposing cells to the SBP1 reaction products, H2 O2 and H2 S were also assessed. In silico analyses identified potential HNF4α Binding sites within the SBP1 promoter region and this was investigated using an inhibitor specific for that transcription factor. RESULTS Using in silico analyses, it was determined that the promoter region of SBP1 contains putative Binding sites for the HNF4α transcription factor. The potential for HNF4α to regulate SBP1 expression was supported by data indicating that HNF4α inhibition resulted in a dose-response increase in the levels of SBP1 messenger RNA and Protein, identifying HNF4α as a novel negative regulator of SBP1 expression in prostate cancer cells. The consequences of altering the levels of SBP1 were investigated by ectopically expressing SBP1 in PC-3 prostate cancer cells, where SBP1 expression attenuated anchorage-independent cellular growth and migration in culture, both properties associated with transformation. SBP1 overexpression reduced oxygen consumption in these cells and increased the activation of AMP-activated Protein kinase (AMPK), a major regulator of energy homeostasis. In addition, the reaction products of SBP1, H2 O2 , and H2 S also activated AMPK. CONCLUSIONS Based on the obtained data, it is hypothesized that SBP1 negatively regulates oxidative phosphorylation (OXPHOS) in the healthy prostate cells by the production of H2 O2 and H2 S and consequential activation of AMPK. The reduction of SBP1 levels in prostate cancer can occur due to increased Binding of HNF4α, acting as a transcriptional inhibitor to the SBP1 promoter. Consequently, there is a reduction in H2 O2 and H2 S-mediated signaling, inhibition of AMPK, and stimulation of OXPHOS and building blocks of biomolecules needed for tumor growth and progression. Other effects of SBP1 loss in tumor cells remain to be discovered.
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Selenium-Binding Protein 1 Reduces Oxygen Consumption and Activates AMPK in Prostate Cancer Cells (OR11-04-19)
Current Developments in Nutrition, 2019Co-Authors: Mostafa Elhodaky, Lenny Hong, Alan M. DiamondAbstract:Abstract Objectives Selenium (Se) is a non-metallic, essential trace element for many organisms, including humans. Se may have potential in cancer prevention, as evidenced by multiple animal and human epidemiological studies. Selenium-Binding Protein 1 (SBP1) is a highly-conserved Protein that covalently binds Se. Prostate cells exhibit cytoplasmic and nuclear SBP1 localization. Reduced levels of nuclear SBP1 were previously shown to be associated with a higher tumor grade and a greater likelihood of prostate cancer recurrence following prostatectomy. The Krebs cycle of the normal prostate is inhibited in favor of the production of citrate energy, therefore distinguishing the energy metabolism of the normal prostate from that of other organs. This inhibition is generally relieved during cancer progression. The objective of this study was to investigate a contribution of SBP1 in this process of metabolic shift. Methods Human PC-3 prostate cancer cells that express very low levels of SBP1 were engineered to express the native, nuclear-targeted, or nuclear-excluded SBP1 by transfection of constitutive- or inducible-SBP1 expression constructs. Oxidative phosphorylation (OXPHOS) was examined by quantifying the oxygen consumption rate (OCR) using a Seahorse XF analyzer (Agilent, Inc.). Western blotting with SBP1 and phospho-AMPK specific antibodies was employed to interrogate the activation of AMP-activated Protein kinase (AMPK), a key regulator of energy homeostasis. Results Overexpressing SBP1 in PC-3 cells increased the activating phosphorylation of AMPK at Thr172 by approximately 70%. In addition, overexpressing the native, nuclear-targeted or nuclear-excluded SBP1 significantly reduced OCR and mitochondrial ATP synthesis, as measures of mitochondrial respiration (32–43% reduction in basal respiration and 40–55% reduction in maximal respiration). These changes in energy metabolism occurred without affecting cellular proliferation. Conclusions These results indicate that the loss of SBP1 during prostate cancer development may contribute to disease progression by facilitating the transition to an energy metabolism that favors increased energy production as well as the building blocks required to sustain tumor growth and survival. Funding Sources National Institute of Health.
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Selenium-Binding Protein 1 in Human Health and Disease.
International journal of molecular sciences, 2018Co-Authors: Mostafa Elhodaky, Alan M. DiamondAbstract:Selenium-Binding Protein 1 (SBP1) is a highly conserved Protein that covalently binds Selenium. SBP1 may play important roles in several fundamental physiological functions, including Protein degradation, intra-Golgi transport, cell differentiation, cellular motility, redox modulation, and the metabolism of sulfur-containing molecules. SBP1 expression is often reduced in many cancer types compared to the corresponding normal tissues and low levels of SBP1 are frequently associated with poor clinical outcome. In this review, the transcriptional regulation of SBP1, the different physiological roles reported for SBP1, as well as the implications of SBP1 function in cancer and other diseases are presented.
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RESEARCH ARTICLE Quantitative Proteomic Analysis Reveals That Anti-Cancer Effects of Selenium-Binding Protein 1 In Vivo Are Associated with Metabolic Pathways
2016Co-Authors: Qi Ying, Alan M. Diamond, Emmanuel Ansong, Wancai YangAbstract:Previous studies have shown the tumor-suppressive role of Selenium-Binding Protein 1 (SBP1), but the underlying mechanisms are unclear. In this study, we found that induction of SBP1 showed significant inhibition of colorectal cancer cell growth and metastasis in mice. We further employed isobaric tags for relative and absolute quantitation (iTRAQ) to identify Proteins that were involved in SBP1-mediated anti-cancer effects in tumor tissues. We identified 132 differentially expressed Proteins, among them, 53 Proteins were upregu-lated and 79 Proteins were downregulated. Importantly, many of the differentially altered Proteins were associated with lipid/glucose metabolism, which were also linked to Glycoly-sis, MAPK, Wnt, NF-kB, NOTCH and epithelial-mesenchymal transition (EMT) signaling pathways. These results have revealed a novel mechanism that SBP1-mediated cancer in-hibition is through altering lipid/glucose metabolic signaling pathways
Jose R. Torrealba - One of the best experts on this subject based on the ideXlab platform.
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Chronic Allograft Vasculopathy Correlates with the Downregulation of Selenium-Binding Protein 1 in Smooth Muscle Cells
American Journal of Clinical Pathology, 2013Co-Authors: Jose R. Torrealba, Drew A. Roenneburg, Arjang DjamaliAbstract:Selenium Binding Protein-1 (SBP-1) has been implicated in intracellular Protein trafficking and secretion. In a rhesus monkey kidney transplant model we previously demonstrated that SBP-1 is significantly downregulated in the smooth muscle cells (SMC) of arteries with chronic allograft vasculopathy (CAV). The purposes of this study were multiple: (1) to investigate the expression of SBP-1 in human and murine allografts with chronic vasculopathy; (2) to explore factors that …
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Selenium Binding Protein 1 in smooth muscle cells is downregulated in a rhesus monkey model of chronic allograft nephropathy
American Journal of Transplantation, 2005Co-Authors: Jose R. Torrealba, Drew A. Roenneburg, Matthew Colburn, Susan Golner, Zhen Chang, Tara L Scheunemann, John H Fechner, Tausif Alam, Hyoung Tae Kim, Turan KanmazAbstract: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.
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Selenium Binding Protein 1: Passive or Active Role in Disease?
American Journal of Transplantation, 2005Co-Authors: Jose R. TorrealbaAbstract:We thankDr.CharlesDiskinforhisencouragingcommentson our work on the involvement of Selenium Binding pro-tein 1 (SBP-1) in chronic renal allograft nephropathy, CAN(1).WeagreewithhisassessmentthatatthispointwecannotconcludewhetherthedecreaseinSBP-1inthesmoothmuscle cells (SMC) of monkeys with CAN is the cause orthe consequence of the renal impairment. It is indeed in-teresting that Selenium increases in vascular diseases (2).We, however, have not examined whether there is a corre-lation between the levels of circulating Selenium in serumor plasma and the levels of the tyrosine-phosphorylatedintra-cytoplasmic SBP-1. Our
Ok-nam Bae - One of the best experts on this subject based on the ideXlab platform.
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Identification of a sensitive urinary biomarker, Selenium-Binding Protein 1, for early detection of acute kidney injury
Journal of toxicology and environmental health. Part A, 2017Co-Authors: Kyeong Seok Kim, Seung Jun Kwack, Ji Yeon Son, Hun Yong Yang, Hosup Song, Ye Rim Kang, Jihoon Kwon, Young Mi Kim, Ok-nam BaeAbstract:Acute kidney injury (AKI) is associated with increased mortality rate in patients but clinically available biomarkers for disease detection are currently not available. Recently, a new biomarker, Selenium-Binding Protein 1 (SBP1), was identified for detection of nephrotoxicity using proteomic analysis. The aim of this study was to assess the sensitivity of urinary SBP1 levels as an early detection of AKI using animal models such as cisplatin or ischemia/reperfusion (I/R). Sprague-Dawley rats were injected with cisplatin (6 mg/kg, once i.p.) and sacrificed at 1, 3, or 5 days after treatment. Ischemia was achieved by bilaterally occluding both kidneys with a microvascular clamp for 45 min and verified visually by a change in tissue color. After post-reperfusion, urine samples were collected at 9, 24, and 48 hr intervals. Urinary excretion of Protein-based biomarkers was measured by Western blot analysis. In cisplatin-treated rats, mild histopathologic alterations were noted at day 1 which became severe at day 3. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at day 3. Levels of urinary excretion of SBP1, neutrophil gelatinase-associated lipocalin (NGAL), and a tissue inhibitor of metalloProteinase-1 (TIMP-1) were markedly elevated at day 3 and 5 following drug treatment. In the vehicle-treated I/R group, serum levels of BUN and SCr and AST activity were significantly increased compared to sham. Urinary excretion of SBP1 and NGAL rose markedly following I/R. The urinary levels of SBP1, NGAL, TIMP-1, and KIM-1 Proteins excreted by AKI patients and normal subjects were compared. Among these Proteins, a marked rise in SBP1 was observed in urine of patients with AKI compared to normal subjects. Based upon receiver-operator curves (ROC), SBP1 displayed a higher area under the curve (AUC) scores than levels of SCr, BUN, total Protein, and glucose. In particular, SBP1 Protein was readily detected in small amounts of urine without purification. Data thus indicate that urinary excretion of SBP1 may be useful as a reliable biomarker for early diagnosis of AKI in patients.
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Selenium-Binding Protein 1: a sensitive urinary biomarker to detect heavy metal-induced nephrotoxicity
Archives of Toxicology, 2017Co-Authors: Eui Kyung Lee, Young-jun Shin, Eun Young Park, Nam Deuk Kim, Aree Moon, Seung Jun Kwack, Ji Yeon Son, Sam Kacew, Byung Mu Lee, Ok-nam BaeAbstract:Identifying novel biomarkers to detect nephrotoxicity is clinically important. Here, we attempted to identify new biomarkers for mercury-induced nephrotoxicity and compared their sensitivity to that of traditional biomarkers in animal models. Comparative proteomics analysis was performed in kidney tissues of Sprague–Dawley rats after oral treatment with HgCl_2 (0.1, 1, or 5 mg/kg/day) for 21 days. Kidney cortex tissues were analyzed by two-dimensional gel electrophoresis/matrix-assisted laser desorption/ionization, and differentially expressed Proteins were identified. The corresponding spots were quantitated by RT-PCR. Selenium-Binding Protein 1 (SBP1) was found to be the most markedly upregulated Protein in the kidney cortex of rats after HgCl_2 administration. However, blood urea nitrogen, serum creatinine, and glucose levels increased significantly only in the 1 or 5 mg/kg HgCl_2-treated groups. A number of urinary excretion Proteins, including kidney injury molecule-1, clusterin, monocyte chemoattractant Protein-1, and β-microglobulin, increased dose-dependently. Histopathological examination revealed severe proximal tubular damage in high-dose (5 mg/kg) HgCl_2-exposed groups. In addition, urinary excretion of SBP1 significantly increased in a dose-dependent manner. To confirm the critical role of SBP1 as a biomarker for nephrotoxicity, normal kidney proximal tubular cells were treated with HgCl_2, CdCl_2, or cisplatin for 24 h. SBP1 levels significantly increased in conditioned media exposed to nephrotoxicants, but decreased in cell lysates. Our investigations suggest that SBP1 may play a critical role in the pathological processes underlying chemical-induced nephrotoxicity. Thus, urinary excretion of SBP1 might be a sensitive and specific biomarker to detect early stages of kidney injury.