Redox Regulation of Protein Tyrosine Phosphatase 1B by Manipulation of Dietary Selenium Affects the Triglyceride Concentration in Rat Liver

Mueller, Andreas S.; Klomann, Sandra D.; Wolf, Nicole M.; Schneider, Sandra; Schmidt, Rupert; Spielmann, Julia; Stangl, Gabriele I.; Eder, Klaus; Pallauf, J.

doi:10.3945/jn.108.089482

Cited by 65 publications

(48 citation statements)

References 85 publications

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“…Glutathione from GPx activity has also been shown to regulate PTP1B activity (45). We observed an increase in GPx1 mRNA levels in the liver of Scly KO mice fed an adequate-Se diet (Table 2), but such increase was not accompanied by its protein levels (Fig.…”

Section: Resultsmentioning

confidence: 57%

Disruption of the Selenocysteine Lyase-Mediated Selenium Recycling Pathway Leads to Metabolic Syndrome in Mice

Seale

Hashimoto

Kurokawa

et al. 2012

Molecular and Cellular Biology

106

102

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Selenium (Se) is an essential trace element used for biosynthesis of selenoproteins and is acquired either through diet or cellular recycling mechanisms. Selenocysteine lyase (Scly) is the enzyme that supplies Se for selenoprotein biosynthesis via decomposition of the amino acid selenocysteine (Sec). Knockout (KO) of Scly in a mouse affected hepatic glucose and lipid homeostasis. Mice lacking Scly and raised on an Se-adequate diet exhibit hyperinsulinemia, hyperleptinemia, glucose intolerance, and hepatic steatosis, with increased hepatic oxidative stress, but maintain selenoprotein levels and circulating Se status. Insulin challenge of Scly KO mice results in attenuated Akt phosphorylation but does not decrease phosphorylation levels of AMP kinase alpha (AMPK␣). Upon dietary Se restriction, Scly KO animals develop several characteristics of metabolic syndrome, such as obesity, fatty liver, and hypercholesterolemia, with aggravated hyperleptinemia, hyperinsulinemia, and glucose intolerance. Hepatic glutathione peroxidase 1 (GPx1) and selenoprotein S (SelS) production and circulating selenoprotein P (Sepp1) levels are significantly diminished. Scly disruption increases the levels of insulin-signaling inhibitor PTP1B. Our results suggest a dependence of glucose and lipid homeostasis on Scly activity. These findings connect Se and energy metabolism and demonstrate for the first time a unique physiological role of Scly in an animal model. S elenium (Se) is an essential trace element acquired through the diet that has been implicated in brain (53), immune, and thyroid function (49), in fertility (2), and in cancer prevention (43). Dietary Se is found in inorganic or organic forms. Se is mostly utilized for biosynthesis of the unique amino acid selenocysteine (Sec), which is cotranslationally incorporated into selenoproteins (36), functioning primarily in redox reactions. The Sec incorporation mechanism involves de novo synthesis of Sec via selenophosphate (SeϳP), which is synthesized by selenophosphate synthetases (SPS) (60). SeϳP is enzymatically attached to the O-phosphoseryl-tRNA, which is then converted to the specific selenocysteyl-tRNA [Ser]Sec used in the selenoprotein translation (54,61). Se is thought to enter the SeϳP pool for Sec biosynthesis either from diet or via recycling after selenoprotein degradation and release of Sec.Selenocysteine lyase (Scly) is responsible for cellular Sec decomposition to mobilize Se for utilization in selenoprotein synthesis (10, 41). Scly was first isolated and characterized from pig liver (18) and subsequently shown to break down Sec into alanine and selenide (41). Scly has been the target of several in vitro studies: it was reported to interact with SPS (58), and its crystal structure revealed the mechanism for the enzyme reaction specificity toward Se (10, 46). In vivo, Scly was recently shown to be involved in selenoprotein biosynthesis in HeLa cells (30). However, the physiological role of Scly in cellular Se metabolism and in vertebrate whole-body Se homeostasis remain...

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Section: Resultsmentioning

confidence: 57%

Disruption of the Selenocysteine Lyase-Mediated Selenium Recycling Pathway Leads to Metabolic Syndrome in Mice

Seale

Hashimoto

Kurokawa

et al. 2012

Molecular and Cellular Biology

106

102

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“…More specifically, the Se-overdosed pigs had >50% plasma insulin levels than the Se-adequate pigs to maintain similar plasma glucose concentrations, indicating an early sign of insulin resistance. Unlike rats [58][59][60], pigs fed the high-Se diet (3 mg of Se/kg of diet) did not develop hyperlipidemia compared with those fed 0.3 mg of Se/kg of diet. Meanwhile, Pinto et al [63] reported that after 16 weeks of intervention, fasting plasma insulin and cholesterol levels were increased in pigs fed 0.50 mg of Se/kg of diet (as Se-yeast) compared with those fed 0.17 mg of Se/kg of diet, although fasting glucose concentrations did not differ between the two groups.…”

Section: Elevations Of Se Intake and Selenoprotein Expression On Diabmentioning

confidence: 99%

“…First, many of the past animal studies used diabetic animals [29][30][31][32][33][34][35][36][37][38][39], but the present studies have been conducted in normal animals [53,[57][58][59][60][62][63]. Second, the past experiments used high or nearly toxic doses of Se (0.9-4.5 mg/kg body weight) [29][30][31][32][33][34][35][36][37][38][39], while recent experiments used Se levels not exceeding their maximal tolerable limits (≤33.0 mg Se/kg diet).…”

Section: Perspective and Conclusionmentioning

confidence: 99%

“…Second, the past experiments used high or nearly toxic doses of Se (0.9-4.5 mg/kg body weight) [29][30][31][32][33][34][35][36][37][38][39], while recent experiments used Se levels not exceeding their maximal tolerable limits (≤33.0 mg Se/kg diet). Finally, many of the past animal studies lasted only 2 to 8 weeks, whereas in most of recent animal studies the duration of Se supplementation has been 12 weeks or longer [53,[57][58][59][60][62][63].…”

Section: Perspective and Conclusionmentioning

confidence: 99%

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Selenium and diabetes - evidence from animal studies

Lei

2012

Free Radical Biology and Medicine

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“…Rats that were fed 75 or 150 μg of selenium/kg showed an increase in thioredoxin reductase, as well as other selenoproteins, and a decrease in PTP1B glutathionylation (which inhibits PTP activity). 285 It is possible that the oxidation of PTPs via the oxidative stress of tamoxifen treatment can play an important role in tamoxifen resistance through lack of interaction with kinases that phosphorylate p27. In the suggested case of an increase oxidized state in the cell by chronic tamoxifen treatment, oxidized Trx is unable to reduce p27-affecting PTPs, which could play a role in the continued growth of cancer cells in the presence of tamoxifen treatment.…”

mentioning

confidence: 99%

Thioredoxin and Jab1 Control Estrogen- and Antiestrogen-Mediated Progression of the Cell Cycle Through p27 Interactions

Penney¹

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A major problem with breast cancer treatment is the prevalence of antiestrogen resistance, be it de novo or acquired after continued use. Many of the underlying mechanisms of antiestrogen resistance are not clear, although estrogen receptor-mediated actions have been identified as a pathway that is blocked by antiestrogens. Selective estrogen receptor modulators (SERMs), such as tamoxifen, are capable of producing reactive oxygen species (ROS) through metabolic activation, and these ROS, at high levels, can induce irreversible growth arrest that is similar to the growth arrest incurred by SERMs. This suggests that SERM-mediated growth arrest may also be through ROS accumulation. Breast cancer receiving long-term antiestrogen treatment appears to adapt to this increased, persistent level of ROS. This, in turn, leads to the disruption of reversible redox signaling that involves redox-sensitive phosphatases and protein kinases and transcription factors. This has downstream consequences for apoptosis, cell cycle progression, and cell metabolism. For this dissertation, we explored if altering the ROS formed by tamoxifen also alters sensitivity of the drug in resistant cells. We explored an vi association with a thioredoxin/Jab1/p27 pathway, and a possible role of dysregulation of thioredoxin-mediated redox regulation contributing to the development of antiestrogen resistance in breast cancer. We used standard laboratory techniques to perform proteomic assays that showed cell proliferation, protein concentrations, redox states, and proteinprotein interactions. We found that increasing thioredoxin reductase levels, and thus increasing the amount of reduced thioredoxin, increased tamoxifen sensitivity in previously resistant cells, as well as altered estrogen and tamoxifen-induced ROS. We also found that decreasing levels of Jab1 protein also increased tamoxifen sensitivity, and that the downstream effects showed a decrease p27 phosphorylation in both cases. We conclude that the chronic use of tamoxifen can lead to an increase in ROS that alters cell signaling and causing cell growth in the presence of tamoxifen, and that this resistant cell growth can be reversed with an alteration to the thioredoxin/Jab1 pathway.

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Redox Regulation of Protein Tyrosine Phosphatase 1B by Manipulation of Dietary Selenium Affects the Triglyceride Concentration in Rat Liver

Cited by 65 publications

References 85 publications

Disruption of the Selenocysteine Lyase-Mediated Selenium Recycling Pathway Leads to Metabolic Syndrome in Mice

Disruption of the Selenocysteine Lyase-Mediated Selenium Recycling Pathway Leads to Metabolic Syndrome in Mice

Selenium and diabetes - evidence from animal studies

Thioredoxin and Jab1 Control Estrogen- and Antiestrogen-Mediated Progression of the Cell Cycle Through p27 Interactions

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