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Susan Kennedy - One of the best experts on this subject based on the ideXlab platform.
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cysteine Sulfinic Acid decarboxylase regulation a role for farnesoid x receptor and small heterodimer partner in murine hepatic taurine metabolism
Hepatology Research, 2014Co-Authors: Thomas A Kerr, Sayeepriyadarshini Anakk, Yuri Matsumoto, Martha H Stipanuk, Lawrence L Hirschberger, Susan Kennedy, David D Moore, Mitsuhiro Watanabe, Hitoshi Matsumoto, Nicholas O DavidsonAbstract:Aim Bile Acid synthesis is regulated by nuclear receptors including farnesoid X receptor (FXR) and small heterodimer partner (SHP), and by fibroblast growth factor 15/19 (FGF15/19). We hypothesized that hepatic cysteine Sulfinic Acid decarboxylase (CSAD) (a key enzyme in taurine synthesis) is regulated by bile Acids (BA). The aim of this study was to investigate CSAD regulation by BA dependent regulatory mechanisms. Methods Mice were fed a control diet or a diet supplemented with either 0.5% cholate or 2% cholestyramine. To study BA dependent pathways, we utilized GW4064 (FXR agonist), FGF19 or T-0901317 (liver X receptor [LXR] agonist) and Shp−/− mice. Tissue mRNA was determined by quantitative reverse transcription polymerase chain reaction. Amino Acids were measured by high-performance liquid chromatography. Results Mice supplemented with dietary cholate exhibited reduced hepatic CSAD mRNA while those receiving cholestyramine exhibited increased mRNA. Activation of FXR suppressed CSAD mRNA expression whereas CSAD expression was increased in Shp−/− mice. Hepatic hypotaurine concentration (the product of CSAD) was higher in Shp−/− mice with a corresponding increase in serum taurine conjugated BA. FGF19 administration suppressed hepatic cholesterol 7-α-hydroxylase (CYP7A1) mRNA but did not change CSAD mRNA expression. LXR activation induced CYP7A1 mRNA yet failed to induce CSAD mRNA expression. Conclusion BA regulate CSAD mRNA expression in a feedback fashion via mechanisms involving SHP and FXR but not FGF15/19 or LXR. These findings implicate BA as regulators of CSAD mRNA via mechanisms shared with CYP7A1.
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cysteine Sulfinic Acid decarboxylase regulation a role for fxr and shp in murine hepatic taurine metabolism
Hepatology Research, 2014Co-Authors: Thomas A Kerr, Sayeepriyadarshini Anakk, Yuri Matsumoto, Martha H Stipanuk, Lawrence L Hirschberger, David D Moore, Mitsuhiro Watanabe, Hitoshi Matsumoto, Yan Xie, Susan KennedyAbstract:Background Bile Acid synthesis is regulated by nuclear receptors including farnesoid X receptor (FXR) and small heterodimer partner (SHP), and by fibroblast growth factor15/19 (FGF15/19). Because bile Acid synthesis involves amino Acid conjugation, we hypothesized that hepatic cysteine Sulfinic Acid decarboxylase (CSAD) (a key enzyme in taurine synthesis) is regulated by bile Acids.
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cysteine Sulfinic Acid decarboxylase regulation a role for farnesoid x receptor and small heterodimer partner in murine hepatic taurine metabolism
Hepatology Research, 2014Co-Authors: Thomas A Kerr, Sayeepriyadarshini Anakk, Yuri Matsumoto, Martha H Stipanuk, Lawrence L Hirschberger, David D Moore, Mitsuhiro Watanabe, Hitoshi Matsumoto, Yan Xie, Susan KennedyAbstract:Background Bile Acid synthesis is regulated by nuclear receptors including farnesoid X receptor (FXR) and small heterodimer partner (SHP), and by fibroblast growth factor15/19 (FGF15/19). Because bile Acid synthesis involves amino Acid conjugation, we hypothesized that hepatic cysteine Sulfinic Acid decarboxylase (CSAD) (a key enzyme in taurine synthesis) is regulated by bile Acids.
Mario Fontana - One of the best experts on this subject based on the ideXlab platform.
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carbonate anion radical generated by the peroxidase activity of copper zinc superoxide dismutase scavenging of radical and protection of enzyme by hypotaurine and cysteine Sulfinic Acid
Advances in Experimental Medicine and Biology, 2017Co-Authors: Alessia Baseggio Conrado, Simonetta Maina, Elisabetta Capuozzo, Antonio Francioso, Luciana Mosca, H Moseley, Mario FontanaAbstract:Copper-zinc superoxide dismutase (SOD) is considered one of the most important mammalian antioxidant defenses and plays a relevant role due to its main function in catalyzing the dismutation of superoxide anion to oxygen and hydrogen peroxide. However, interaction between SOD and H2O2 produced a strong copper-bound oxidant (Cu(II)•OH) that seems able to contrast the self-inactivation of the enzyme or oxidize other molecules through its peroxidase activity. The bicarbonate presence enhances the peroxidase activity and produces the carbonate anion radical (CO3•–). CO3 •– is a freely diffusible reactive species capable of oxidizing several molecules that are unwieldy to access into the reactive site of the enzyme. Cu(II)•OH oxidizes bicarbonate to the CO3•–, which spreads out of the binding site and oxidizes hypotaurine and cysteine Sulfinic Acid to the respective sulfonates through an efficient reaction. These findings suggest a defense role for sulfinates against the damage caused by CO3 •– . The effect of hypotaurine and cysteine Sulfinic Acid on the CO3•–-mediated oxidation of the peroxidase probe ABTS to ABTS cation radical (ABTS•+) has been studied. Both sulfinates are able to inhibit the oxidation of ABTS mediated by CO3•–. The effect of hypotaurine and cysteine Sulfinic Acid against SOD inactivation by H2O2 (~42% protection of enzyme activity) has also been investigated. Interestingly, hypotaurine and cysteine Sulfinic Acid partially avoid the H2O2-mediated SOD inactivation, suggesting that the two sulfinates may have access to the SOD reactive site and preserve it by reacting with the copper-bound oxidant. In this way hypotaurine and cysteine Sulfinic Acid not only intercept CO3•– which could move out from the reactive site and cause oxidative damage, but also prevents the inactivation of SOD.
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oxidation of hypotaurine and cysteine Sulfinic Acid by peroxidase generated reactive species
Advances in Experimental Medicine and Biology, 2015Co-Authors: Alessia Baseggio Conrado, Laura Pecci, Elisabetta Capuozzo, Mario FontanaAbstract:Hypotaurine (HTAU) and cysteine Sulfinic Acid (CSA) are the metabolic intermediates in the mammalian pathway leading from cysteine to taurine. Strong evidence has been presented that the formation of taurine (TAU) and cysteic Acid (CA) is the result of the interaction of both sulfinates with various oxidizing agents that may be present in biological systems. The purpose of the present study is to investigate the oxidation of sulfinates, HTAU and CSA, by peroxidase-generated reactive species. Reactive nitrogen and oxygen species can be produced during the process of nitrite oxidation catalyzed by heme peroxidases, such as horseradish peroxidase (HRP) or myeloperoxidase, in the presence of hydrogen peroxide (H2O2). Nitrite is the major end product of nitric oxide (NO) metabolism. Oxidation of nitrite by such mechanisms could be important at sites of inflammatory processes. The formation of reactive nitrogen species (RNS) via peroxidase-catalyzed oxidation of nitrite could represent an additional mechanism of the formation of taurine. The oxidation of the sulfinates, HTAU and CSA, by HRP/H2O2/nitrite system has been evaluated by monitoring the oxygen consumption and the production of the corresponding sulfonates, TAU and CA. Moreover, the effect of HTAU and CSA, on nitrotyrosine formation by HRP/H2O2/nitrite system has been studied. During the HRP/H2O2-dependent oxidation of tyrosine, tyrosyl radicals are formed. The results provide evidence that sulfinates inhibit nitrotyrosine formation not only by scavenging RNS but also by reducing the peroxidase-generated tyrosyl radical.
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reactivity of hypotaurine and cysteine Sulfinic Acid toward carbonate radical anion and nitrogen dioxide as explored by the peroxidase activity of cu zn superoxide dismutase and by pulse radiolysis
Free Radical Research, 2014Co-Authors: Baseggio A Conrado, Laura Pecci, M Dangelantonio, Armida Torreggiani, Mario FontanaAbstract:AbstractHypotaurine and cysteine Sulfinic Acid are known to be readily oxidized to the respective sulfonates, taurine and cysteic Acid, by several oxidative agents that may be present in biological systems. In this work, the relevance of both the carbonate anion and nitrogen dioxide radicals in the oxidation of hypotaurine and cysteine Sulfinic Acid has been explored by the peroxidase activity of Cu,Zn superoxide dismutase (SOD) and by pulse radiolysis. The extent of sulfinate oxidation induced by the system SOD/H2O2 in the presence of bicarbonate (CO3•– generation), or nitrite (•NO2 generation) has been evaluated. Hypotaurine is efficiently oxidized by the carbonate radical anion generated by the peroxidase activity of Cu,Zn SOD. Pulse radiolysis studies have shown that the carbonate radical anion reacts with hypotaurine more rapidly (k = 1.1 × 109 M−1s−1) than nitrogen dioxide (k = 1.6 × 107 M−1s−1). Regarding cysteine Sulfinic Acid, it is less reactive with the carbonate radical anion (k = 5.5 × 107 M−...
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reactivity of hypotaurine and cysteine Sulfinic Acid toward carbonate radical anion and nitrogen dioxide as explored by the peroxidase activity of cu zn superoxide dismutase and by pulse radiolysis
Free Radical Research, 2014Co-Authors: Baseggio A Conrado, Laura Pecci, M Dangelantonio, Armida Torreggiani, Mario FontanaAbstract:Hypotaurine and cysteine Sulfinic Acid are known to be readily oxidized to the respective sulfonates, taurine and cysteic Acid, by several oxidative agents that may be present in biological systems. In this work, the relevance of both the carbonate anion and nitrogen dioxide radicals in the oxidation of hypotaurine and cysteine Sulfinic Acid has been explored by the peroxidase activity of Cu,Zn superoxide dismutase (SOD) and by pulse radiolysis. The extent of sulfinate oxidation induced by the system SOD/H2O2 in the presence of bicarbonate (CO3(•-) generation), or nitrite ((•)NO2 generation) has been evaluated. Hypotaurine is efficiently oxidized by the carbonate radical anion generated by the peroxidase activity of Cu,Zn SOD. Pulse radiolysis studies have shown that the carbonate radical anion reacts with hypotaurine more rapidly (k = 1.1 × 10(9) M(-1)s(-1)) than nitrogen dioxide (k = 1.6 × 10(7) M(-1)s(-1)). Regarding cysteine Sulfinic Acid, it is less reactive with the carbonate radical anion (k = 5.5 × 10(7) M(-1)s(-1)) than hypotaurine. It has also been observed that the one-electron transfer oxidation of both sulfinates by the radicals is accompanied by the generation of transient sulfonyl radicals (RSO2(•)). Considering that the carbonate radical anion could be formed in vivo at high level from bicarbonate, this radical can be included in the oxidants capable of performing the last metabolic step of taurine biosynthesis. Moreover, the protective effect exerted by hypotaurine and cysteine sulfinate on the carbonate radical anion-mediated tyrosine dimerization indicates that both sulfinates have scavenging activity towards the carbonate radical anion. However, the formation of transient reactive intermediates during sulfinate oxidation by carbonate anion and nitrogen dioxide radical may at the same time promote oxidative reactions.
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the reactivity of hypotaurine and cysteine Sulfinic Acid with peroxynitrite
Advances in Experimental Medicine and Biology, 2006Co-Authors: Mario Fontana, Silvestro Dupre, Laura PecciAbstract:The oxidation of the Sulfinic group of both hypotaurine and cysteine Sulfinic Acid with production of the respective sulfonate, taurine and cysteic Acid is a crucial point for the generation of taurine in mammalian tissues (Wright et al., 1986; Huxtable, 1992). It has been proposed that the high levels of taurine found in tissues or cells such as sperm, neutrophils and retinal tissue (Pasantes-Morales et al., 1972; Alvarez and Storey, 1983; Learn et al., 1990; Green et al., 1991; Holmes et al., 1992) would reflect the turnover of hypotaurine via oxidative reactions and might be viewed as an indirect measure of the oxidative stress associated with such tissues. However, the mechanism of the oxidative reaction of the Sulfinic group is not yet clearly defined. Recently, it has been shown that, besides nonspecific oxidants such as UV irradiation, hypochlorite, hydroxyl radical and photochemically generated singlet oxygen, also peroxynitrite mediates the oxidation of both hypotaurine and cysteine Sulfinic Acid to taurine and cysteic Acid, respectively (Ricci et al., 1978; Green et al., 1985; Fellman et al., 1987; Pecci et al., 1999; Fontana et al., 2005). These findings have been related to the proposed role of hypotaurine as an antioxidant and free radical trapping agent in vivo (Aruoma et al., 1988; Tadolini et al., 1995). According to this, hypotaurine and cysteine Sulfinic Acid are able to prevent peroxynitrite-mediated reactions such as tyrosine nitration, α1-antiproteinase inactivation and low-density lipoprotein oxidative modification (Fontana et al., 2004). Peroxynitrite is a strong oxidizing and nitrating agent, which can be produced by the reaction of nitric oxide with superoxide anion (Koppenol et al., 1992; Huie and Padmaja, 1993; Pryor and Squadrito, 1995) and represents a reactive toxic species that can mediate cellular and tissue damage in various human diseases, including neurodegenerative disorders, inflammatory and autoimmune diseases (Eiserich et al., 1998; Stewart and Heales, 2003). At physiological pH both peroxynitrite anion (ONOO) and its conjugate
Sue Goo Rhee - One of the best experts on this subject based on the ideXlab platform.
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Sestrin 2 is not a reductase for cysteine Sulfinic Acid of peroxiredoxins.
Antioxidants & redox signaling, 2009Co-Authors: Hyun Ae Woo, Soo Han Bae, Sunjoo Park, Sue Goo RheeAbstract:Abstract The active-site cysteine of 2-Cys peroxiredoxins (Prxs), a subgroup of the Prx family, is reversibly hyperoxidized to cysteine Sulfinic Acid during catalysis with concomitant loss of peroxidase activity. The reduction of Sulfinic 2-Cys Prx enzymes, the first known biologic of such a reaction, has been reported to be catalyzed by either sulfiredoxin (Srx) or sestrin (Sesn) 2. The 13-kDa Srx and 60-kDa Sesn 2 show no sequence similarity, however. Whereas the reductase function of Srx has been confirmed by several studies, such is not the case for Sesn 2. We have now shown that (a) recombinant Sesn 2 did not catalyze the reduction of Sulfinic Prx I in vitro, whereas Srx did; (b) overexpression of Sesn 2 in HeLa or A549 cells did not affect the reduction of 2-Cys Prxs, whereas overexpression of Srx markedly increased the reduction rate; and (c) the rate of Sulfinic 2-Cys Prx reduction in embryonic fibroblasts derived from Sesn 2–knockout mice did not differ from that in those derived from wild-type m...
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sulfiredoxin the cysteine Sulfinic Acid reductase specific to 2 cys peroxiredoxin its discovery mechanism of action and biological significance
Kidney International, 2007Co-Authors: Sue Goo Rhee, Woojin Jeong, Tong-shin ChangAbstract:Peroxiredoxin (Prx) is a family of bifunctional proteins that exhibit peroxidase and chaperone activities. Prx proteins contain a conserved Cys residue that undergoes a redox change between thiol and disulfide states. 2-Cys Prx enzymes, a subgroup of Prx family, are intrinsically susceptible to reversible hyperoxidation to cysteine Sulfinic Acid during catalysis. Cysteine hyperoxidation of Prx was shown to result in loss of peroxidase activity and a concomitant gain of chaperone activity. Reduction of Sulfinic Prx enzymes, the first known biological example of such a reaction, is catalyzed by sulfiredoxin (Srx) in the presence of ATP. Srx appears to exist solely to support the reversible Sulfinic modification of 2-Cys Prx enzymes. Srx specifically binds to 2-Cys Prx enzymes by recognizing several critical surface-exposed residues of the Prxs, and transfer the γ -phosphate of ATP to their Sulfinic moiety, using its conserved cysteine as the phosphate carrier. The resulting Sulfinic phosphoryl ester is reduced to cysteine after oxidation of four thiol equivalents.
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Molecular Mechanism of the Reduction of Cysteine Sulfinic Acid of Peroxiredoxin to Cysteine by Mammalian Sulfiredoxin
The Journal of biological chemistry, 2006Co-Authors: Woojin Jeong, Sung Jun Park, Tong-shin Chang, Duck-yeon Lee, Sue Goo RheeAbstract:Abstract Among many proteins with cysteine Sulfinic Acid (Cys-SO2H) residues, the Sulfinic forms of certain peroxiredoxins (Prxs) are selectively reduced by sulfiredoxin (Srx) in the presence of ATP. All Srx enzymes contain a conserved cysteine residue. To elucidate the mechanism of the Srx-catalyzed reaction, we generated various mutants of Srx and examined their interaction with PrxI, their ATPase activity, and their ability to reduce Sulfinic PrxI. Our results suggest that three surface-exposed amino Acid residues, corresponding to Arg50, Asp57, and Asp79 of rat Srx, are critical for substrate recognition. The presence of the Sulfinic form (but not the reduced form) of PrxI induces the conserved cysteine of Srx to take the γ-phosphate of ATP and then immediately transfers the phosphate to the Sulfinic moiety of PrxI to generate a Sulfinic Acid phosphoryl ester (Prx-Cys-S(=O)). This ester is reductively cleaved by a thiol molecule (RSH) such as GSH, thioredoxin, and dithiothreitol to produce a disulfide-S-monoxide (Prx-Cys-S(=O)-S-R). The disulfide-S-monoxide is further reduced through the oxidation of three thiol equivalents to complete the catalytic cycle and regenerate Prx-Cys-SH.
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Reduction of Cysteine Sulfinic Acid by Sulfiredoxin Is Specific to 2-Cys Peroxiredoxins
The Journal of biological chemistry, 2004Co-Authors: Hyun Ae Woo, Woojin Jeong, Sung Jun Park, Tong-shin Chang, Kwang Joo Park, Jeong Soo Yang, Sue Goo RheeAbstract:Abstract Cysteine residues of certain peroxiredoxins (Prxs) undergo reversible oxidation to Sulfinic Acid (Cys-SO2H) and the reduction reaction is catalyzed by sulfiredoxin (Srx). Specific Cys residues of various other proteins are also oxidized to Sulfinic Acid, suggesting that formation of Cys-SO2H might be a novel posttranslational modification that contributes to regulation of protein function. To examine the susceptibility of Sulfinic forms of proteins to reduction by Srx, we prepared such forms of all six mammalian Prx isoforms and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Purified sulfiredoxin reduced the Sulfinic forms of the four 2-Cys members (Prx I to Prx IV) of the Prx family in vitro, but it did not affect those of Prx V, Prx VI, or GAPDH. Furthermore, Srx bound specifically to the four 2-Cys Prxs in vitro and in cells. Sulfinic forms of Prx I and Prx II, but not of Prx VI or GAPDH, present in H2O2-treated A549 cells were gradually reduced after removal of H2O2; overexpression of Srx increased the rate of the reduction of Prx I and Prx II but did not induce that of Prx VI or GAPDH. These results suggest that reduction of Cys-SO2H by Srx is specific to 2-Cys Prx isoforms. For proteins such as Prx VI and GAPDH, Sulfinic Acid formation might be an irreversible process that causes protein damage.
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characterization of mammalian sulfiredoxin and its reactivation of hyperoxidized peroxiredoxin through reduction of cysteine Sulfinic Acid in the active site to cysteine
Journal of Biological Chemistry, 2004Co-Authors: Tong-shin Chang, Woojin Jeong, Sunjoo Park, Sue Goo RheeAbstract:Abstract Peroxiredoxins (Prxs) are a family of peroxidases that reduce hydroperoxides. The cysteine residue in the active site of certain eukaryotic Prx enzymes undergoes reversible oxidation to Sulfinic Acid (Cys-SO2H) during catalysis, and sulfiredoxin (Srx) has been identified as responsible for reversal of the resulting enzyme inactivation in yeast. We have now characterized mammalian orthologs of yeast Srx with an assay based on monitoring of the reduction of Sulfinic Prx by immunoblot analysis with antibodies specific for the Sulfinic state. Sulfinic reduction by mammalian Srx was found to be a slow process (kcat = 0.18/min) that requires ATP hydrolysis. ATP could be efficiently replaced by GTP, dATP, or dGTP but not by CTP, UTP, dCTP, or dTTP. Both glutathione and thioredoxin are potential physiological electron donors for the Srx reaction, given that their Km values (1.8 mm and 1.2 μm, respectively) are in the range of their intracellular concentrations, and the Vmax values obtained with the two reductants were similar. Although its pKa is relatively low (∼7.3), the active site cysteine of Srx remained reduced even when the active site cysteine of most Prx molecules became oxidized. Finally, depletion of human Srx by RNA interference suggested that Srx is largely responsible for reduction of the Cys-SO2H of Prx in A549 human cells.
Georgia Schuller-levis - One of the best experts on this subject based on the ideXlab platform.
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A Novel Cysteine Sulfinic Acid Decarboxylase Knock-Out Mouse: Taurine Distribution in Various Tissues With and Without Taurine Supplementation
Advances in experimental medicine and biology, 2017Co-Authors: Eunkyue Park, Seung Yong Park, In Soo Cho, Bo Sook Kim, Georgia Schuller-levisAbstract:Taurine, a sulfur containing amino Acid, has various physiological functions including development of the eye and brain, immune function, reproduction, osmo-regulatory function as well as anti-oxidant and anti-inflammatory activities. In order to understand the physiological role, we developed taurine deficient mice deleting a rate-liming enzyme, cysteine Sulfinic Acid decarboxylase (CSAD) for biosynthesis of taurine. Taurine was measured in various tissues including the liver, brain, lung, spleen, thymus, pancreas, heart, muscle and kidney as well as plasma from CSAD knock-out mice (CSAD KO) with and without treatment of taurine in the drinking water at the age of 2 months (2 M). Taurine was determined using HPLC as a phenylisothiocyanate derivative of taurine at 254 nm. Taurine concentrations in the liver and kidney from homozygotes of CSAD KO (HO), in which CSAD level is high, were 90% and 70% lower than WT, respectively. Taurine concentrations in the brain, spleen and lung, where CSAD level is low, were 21%, 20% and 28% lower than WT, respectively. At 2 M, 1% taurine treatment of HO restored taurine concentrations in all tissues compared to that of WT. To select an appropriate taurine treatment, HO were treated with various concentrations (0.05, 0.2, 1%) of taurine for 4 months (4 M). Restoration of taurine in all tissues except the liver, kidney and lung requires 0.05% taurine to be restored to that of WT. The liver and kidney restore taurine back to WT with 0.2% taurine. To examine which enzymes influence taurine concentrations in various tissues from WT and HO at 2 M, expression of five taurine-related enzymes, two antioxidant enzymes as well as lactoferrin (Lft) and prolactin receptor (Prlr) was determined using RT2 qPCR. The expression of taurine transporter in the liver, brain, muscle and kidney from HO was increased except in the lung. Our data showed expression of glutamate decarboxylase-like 1(Gadl-1) was increased in the brain and muscle in HO, compared to WT, indicating taurine in the brain and muscle from HO was replenished through taurine transporter and increased biosynthesis of taurine by up-regulated Gadl-1. The expression of glutathione peroxidase 3 was increased in the brain and peroxireductase 2 was increased in the liver and lung, suggesting taurine has anti-oxidant activity. In contrast to newborn and 1 month CSAD KO, Ltf and Prlr in the liver from CSAD KO at 2 M were increased more than two times and 52%, respectively, indicating these two proteins may be required for pregnancy of CSAD KO. Ltf in HOT1.0 was restored to WT, while Prlr in HOT1.0 was increased more than HO, explaining improvement of neonatal survival with taurine supplementation.
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A novel cysteine Sulfinic Acid decarboxylase knock-out mouse: comparison between newborn and weanling mice.
Advances in experimental medicine and biology, 2015Co-Authors: Eunkyue Park, Seung Yong Park, Carl Dobkin, Georgia Schuller-levisAbstract:We developed a novel cysteine Sulfinic Acid decarboxylase knockout mouse (CSAD KO) to investigate the critical roles of taurine. The absence of the CSAD gene was confirmed using Southern, northern and western blotting; homozygous (CSAD−/−) and heterozygous (CSAD+/-) animals were identified using PCR. Plasma taurine concentrations were decreased by 86 % in CSAD−/− animals. Reproductive performance was poor in the second and later CSAD−/− generations but was restored by supplementing the drinking water with 0.05 % taurine. Taurine concentrations at postnatal day 1 (PD1) in generation 1 (G1) CSAD−/− were close to normal presumably due to taurine transport through the placenta from the CSAD+/− dam. In contrast, taurine concentrations in the brain and liver of G2, G3, and G4 CSAD−/− were very low at birth. At 1 month of age (1 M), 1 week after weaning, the G1 CSAD−/− taurine concentration in the liver decreased to the same level as G2, G3, and G4 CSAD−/−. Taurine concentrations in all CSAD−/− at 1 M were reduced to 44 % of WT in the brain and 5 % in the liver. Taurine supplementation restored brain levels to 76 % of WT but had little effect on the liver. Gene expression in CSAD−/− brain and liver was compared to WT at PD1 and 1 M. Expression of the prolactin receptor and lactoferrin genes was decreased in CSAD−/− at both PD1 and 1 M. Metabolic genes including serine dehydratase and uridine phosphorylase 2 were increased significantly at PD1 but not at 1 M. An oxidative stress gene, glutathioneperoxidase 3 was increased in CSAD KO−/− at both PD1 and 1 M. Expression of taurine metabolism genes, cysteine dioxygenase (Cdo), cysteamine dioxygenase and the taurine transporter (TauT) were unaffected at PD1. At 1 M, however, TauT in CSAD−/− liver was increased twofold, while Cdo was decreased compared to WT. These data indicate that the CSAD KO mouse is a powerful model for exploring the role of taurine deficiency in various disorders especially since the requirement for taurine can be supplied in food or water.
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Cloning of murine cysteine Sulfinic Acid decarboxylase and its mRNA expression in murine tissues
Biochimica et biophysica acta, 2002Co-Authors: Eunkyue Park, Seung Yong Park, Chuanhua Wang, Giuseppe Lafauci, Georgia Schuller-levisAbstract:Cysteine Sulfinic Acid decarboxylase (CSD) is the rate-limiting enzyme for biosynthesis of taurine which is essential to biological processes such as development of the brain and eye, reproduction, osmoregulation as well as the anti-inflammatory activity of leukocytes. We report the cDNA sequence of murine CSD that predicts a polypeptide of 493 amino Acids. This protein shares 98% and 90% of amino Acids with rat and human CSD, respectively, indicating that it is a true ortholog of CSD. Northern blot analysis revealed that CSD mRNA is expressed in kidney and liver, and was not detected in lymphoid tissues and lung. The nucleotide sequence of murine CSD should be useful for genetic manipulation of the CSD gene.
Thomas A Kerr - One of the best experts on this subject based on the ideXlab platform.
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cysteine Sulfinic Acid decarboxylase regulation a role for farnesoid x receptor and small heterodimer partner in murine hepatic taurine metabolism
Hepatology Research, 2014Co-Authors: Thomas A Kerr, Sayeepriyadarshini Anakk, Yuri Matsumoto, Martha H Stipanuk, Lawrence L Hirschberger, Susan Kennedy, David D Moore, Mitsuhiro Watanabe, Hitoshi Matsumoto, Nicholas O DavidsonAbstract:Aim Bile Acid synthesis is regulated by nuclear receptors including farnesoid X receptor (FXR) and small heterodimer partner (SHP), and by fibroblast growth factor 15/19 (FGF15/19). We hypothesized that hepatic cysteine Sulfinic Acid decarboxylase (CSAD) (a key enzyme in taurine synthesis) is regulated by bile Acids (BA). The aim of this study was to investigate CSAD regulation by BA dependent regulatory mechanisms. Methods Mice were fed a control diet or a diet supplemented with either 0.5% cholate or 2% cholestyramine. To study BA dependent pathways, we utilized GW4064 (FXR agonist), FGF19 or T-0901317 (liver X receptor [LXR] agonist) and Shp−/− mice. Tissue mRNA was determined by quantitative reverse transcription polymerase chain reaction. Amino Acids were measured by high-performance liquid chromatography. Results Mice supplemented with dietary cholate exhibited reduced hepatic CSAD mRNA while those receiving cholestyramine exhibited increased mRNA. Activation of FXR suppressed CSAD mRNA expression whereas CSAD expression was increased in Shp−/− mice. Hepatic hypotaurine concentration (the product of CSAD) was higher in Shp−/− mice with a corresponding increase in serum taurine conjugated BA. FGF19 administration suppressed hepatic cholesterol 7-α-hydroxylase (CYP7A1) mRNA but did not change CSAD mRNA expression. LXR activation induced CYP7A1 mRNA yet failed to induce CSAD mRNA expression. Conclusion BA regulate CSAD mRNA expression in a feedback fashion via mechanisms involving SHP and FXR but not FGF15/19 or LXR. These findings implicate BA as regulators of CSAD mRNA via mechanisms shared with CYP7A1.
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cysteine Sulfinic Acid decarboxylase regulation a role for fxr and shp in murine hepatic taurine metabolism
Hepatology Research, 2014Co-Authors: Thomas A Kerr, Sayeepriyadarshini Anakk, Yuri Matsumoto, Martha H Stipanuk, Lawrence L Hirschberger, David D Moore, Mitsuhiro Watanabe, Hitoshi Matsumoto, Yan Xie, Susan KennedyAbstract:Background Bile Acid synthesis is regulated by nuclear receptors including farnesoid X receptor (FXR) and small heterodimer partner (SHP), and by fibroblast growth factor15/19 (FGF15/19). Because bile Acid synthesis involves amino Acid conjugation, we hypothesized that hepatic cysteine Sulfinic Acid decarboxylase (CSAD) (a key enzyme in taurine synthesis) is regulated by bile Acids.
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cysteine Sulfinic Acid decarboxylase regulation a role for farnesoid x receptor and small heterodimer partner in murine hepatic taurine metabolism
Hepatology Research, 2014Co-Authors: Thomas A Kerr, Sayeepriyadarshini Anakk, Yuri Matsumoto, Martha H Stipanuk, Lawrence L Hirschberger, David D Moore, Mitsuhiro Watanabe, Hitoshi Matsumoto, Yan Xie, Susan KennedyAbstract:Background Bile Acid synthesis is regulated by nuclear receptors including farnesoid X receptor (FXR) and small heterodimer partner (SHP), and by fibroblast growth factor15/19 (FGF15/19). Because bile Acid synthesis involves amino Acid conjugation, we hypothesized that hepatic cysteine Sulfinic Acid decarboxylase (CSAD) (a key enzyme in taurine synthesis) is regulated by bile Acids.
