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Young Shik Park - One of the best experts on this subject based on the ideXlab platform.
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Role of Phe-99 and Trp-196 of Sepiapterin reductase from Chlorobium tepidum in the production of L-threo-tetrahydrobiopterin
Acta biochimica et biophysica Sinica, 2008Co-Authors: Supangat, Young Shik Park, Sun Ok Park, Kyung Hye Seo, Sang Yeol Lee, Kon Ho LeeAbstract:Sepiapterin reductase from Chlorobium tepidum (cSR) catalyzes the synthesis of a distinct tetrahydrobiopterin (BH4), L-threo-BH4, different from the mammalian enzyme product. The 3-D crystal structure of cSR has revealed that the product configuration is determined solely by the substrate binding mode within the well-conserved catalytic triads. In cSR, the Sepiapterin is stacked between two aromatic side chains of Phe-99 and Trp-196 and rotated approximately 180o around the active site from the position in mouse Sepiapterin reductase. To confirm their roles in substrate binding, we mutated Phe-99 and/or Trp-196 to alanine (F99A, W196A) by site-directed mutagenesis and comparatively examined substrate binding of the purified proteins by kinetics analysis and differential scanning calorimetry. These mutants had higher Km values than the wild type. Remarkably, the W196A mutation resulted in a higher Km increase compared with the F99A mutation. Consistent with the results, the melting temperature (Tm) in the presence of Sepiapterin was lower in the mutant proteins and the worst was W196A. These findings indicate that the two residues are indispensable for substrate binding in cSR, and Trp-196 is more important than Phe-99 for different stereoisomer production.
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Structure of Chlorobium tepidum Sepiapterin reductase complex reveals the novel substrate binding mode for stereospecific production of L-threo-tetrahydrobiopterin.
The Journal of biological chemistry, 2005Co-Authors: Supangat Supangat, Yong Kee Choi, Young Shik Park, Kyung Hye Seo, Daeyoung Son, Chang-deok Han, Kon Ho LeeAbstract:Sepiapterin reductase (SR) is involved in the last step of tetrahydrobiopterin (BH(4)) biosynthesis by reducing the di-keto group of 6-pyruvoyl tetrahydropterin. Chlorobium tepidum SR (cSR) generates a distinct BH(4) product, L-threo-BH(4) (6R-(1'S,2'S)-5,6,7,8-BH(4)), whereas animal enzymes produce L-erythro-BH(4) (6R-(1'R,2'S)-5,6,7,8-BH(4)) although it has high amino acid sequence similarities to the other animal enzymes. To elucidate the structural basis for the different reaction stereospecificities, we have determined the three-dimensional structures of cSR alone and complexed with NADP and Sepiapterin at 2.1 and 1.7 A resolution, respectively. The overall folding of the cSR, the binding site for the cofactor NADP(H), and the positions of active site residues were quite similar to the mouse and the human SR. However, significant differences were found in the substrate binding region of the cSR. In comparison to the mouse SR complex, the Sepiapterin in the cSR is rotated about 180 degrees around the active site and bound between two aromatic side chains of Trp-196 and Phe-99 so that its pterin ring is shifted to the opposite side, but its side chain position is not changed. The swiveled Sepiapterin binding results in the conversion of the side chain configuration, exposing the opposite face for hydride transfer from NADPH. The different Sepiapterin binding mode within the conserved catalytic architecture presents a novel strategy of switching the reaction stereospecificities in the same protein fold.
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Escherichia coli 6-pyruvoyltetrahydropterin synthase ortholog encoded by ygcM has a new catalytic activity for conversion of Sepiapterin to 7,8-dihydropterin.
FEBS letters, 2002Co-Authors: Hyun Joo Woo, Jee Yun Kang, Yong Kee Choi, Yoon Kyung Hwang, Yeon Jung Kim, Chun Gyu Kim, Young Shik ParkAbstract:The putative gene (ygcM) of Escherichia coli was verified in vitro to encode the ortholog of 6-pyruvoyltetrahydropterin synthase (PTPS). Unexpectedly, the enzyme was found to convert Sepiapterin to 7,8-dihydropterin without any cofactors. The enzymatic product 7,8-dihydropterin was identified by HPLC and mass spectrometry analyses, suggesting a novel activity of the enzyme to cleave the C6 side chain of Sepiapterin. The optimal activity occurred at pH 6.5-7.0. The reaction rate increased up to 3.2-fold at 60-80 degrees C, reflecting the thermal stability of the enzyme. The reaction required no metal ion and was activated slightly by low concentrations (1-5 mM) of EDTA. The apparent K(m) value for Sepiapterin was determined as 0.92 mM and the V(max) value was 151.3 nmol/min/mg. The new catalytic function of E. coli PTPS does not imply any physiological role, because Sepiapterin is not an endogenous substrate of the organism. The same activity, however, was also detected in a PTPS ortholog of Synechocystis sp. PCC 6803 but not significant in Drosophila and human enzymes, suggesting that the activity may be prevalent in bacterial PTPS orthologs.
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Escherichia coli 6-pyruvoyltetrahydropterin synthase ortholog encoded by ygcM has a new catalytic activity for conversion of Sepiapterin to 7,8-dihydropterin.
FEBS Letters, 2002Co-Authors: Hyun Joo Woo, Jee Yun Kang, Yong Kee Choi, Yoon Kyung Hwang, Yeon Jung Kim, Chun Gyu Kim, Young Shik ParkAbstract:The putative gene (ygcM )o fEscherichia coli was veri¢ed in vitro to encode the ortholog of 6-pyruvoyltetrahy- dropterin synthase (PTPS). Unexpectedly, the enzyme was found to convert Sepiapterin to 7,8-dihydropterin without any cofactors. The enzymatic product 7,8-dihydropterin was identi- ¢ed by HPLC and mass spectrometry analyses, suggesting a novel activity of the enzyme to cleave the C6 side chain of Sepiapterin. The optimal activity occurred at pH 6.5^7.0. The reaction rate increased up to 3.2-fold at 60^80‡C, re£ecting the thermal stability of the enzyme. The reaction required no metal ion and was activated slightly by low concentrations (1^5 mM) of EDTA. The apparent Km value for Sepiapterin was deter- mined as 0.92 mM and the Vmax value was 151.3 nmol/min/ mg. The new catalytic function of E. coli PTPS does not imply any physiological role, because Sepiapterin is not an endogenous substrate of the organism. The same activity, however, was also detected in a PTPS ortholog of Synechocystis sp. PCC 6803 but not signi¢cant in Drosophila and human enzymes, suggest- ing that the activity may be prevalent in bacterial PTPS orthologs. 7 2002 Federation of European Biochemical Soci- eties. Published by Elsevier Science B.V. All rights reserved.
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Production of Sepiapterin in Escherichia coli by coexpression of cyanobacterial GTP cyclohydrolase I and human 6-pyruvoyltetrahydropterin synthase.
Applied and environmental microbiology, 2002Co-Authors: Hyun Joo Woo, Jee Yun Kang, Yong Kee Choi, Young Shik ParkAbstract:Synechocystis sp. strain PCC 6803 GTP cyclohydrolase I and human 6-pyruvoyltetrahydropterin synthase were coexpressed in Escherichia coli. The E. coli transformant produced Sepiapterin, which was identified by high-performance liquid chromatography and enzymatically converted to dihydrobiopterin by Sepiapterin reductase. Aldose reductase, another indispensable enzyme for Sepiapterin production, may be endogenous in E. coli.
Jeffrey D. Laskin - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of Sepiapterin Mediated Formation of Dihydrobiopterin and Chemical Redox Cycling by Sulfa Drugs
The FASEB Journal, 2015Co-Authors: Shaojun Yang, Yi Hua Jan, Vladimir Mishin, Diane E. Heck, Debra L. Laskin, Jason R. Richardson, Ned D. Heindel, Jeffrey D. LaskinAbstract:Sepiapterin reductase (SPR) catalyzes the reduction of Sepiapterin to dihydrobiopterin (BH2), a precursor for tetrahydrobiopterin (BH4), a cofactor critical for nitric oxide biosynthesis and alkylglycerol and aromatic amino acid metabolism. SPR also mediates chemical redox cycling, catalyzing one electron reduction of redox active chemicals including quinones; rapid reaction of these radicals with molecular oxygen generates reactive oxygen species (ROS). Using recombinant human SPR, sulfonamide and sulfonylurea based sulfa drugs were found to be potent non-competitive inibitors of both Sepiapterin reduction and redox cycling. The most active inhibitors of Sepiapterin reduction (IC50's = 31-180 nM) were sulfasalazine, sulfathiazole, sulfapyridine, sulfamethoxazole and chlorpropamide. Higher concentrations of the sulfa drugs (IC50's = 0.37-19.4 µM) were required to inhibit redox cycling. In PC12 cells, which generate catecholamine and monoamine neurotransmitters via BH4-dependent amino acid hydroxylases, su...
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Sulfa Drugs Inhibit Sepiapterin Reduction and Chemical Redox Cycling by Sepiapterin Reductase
The Journal of pharmacology and experimental therapeutics, 2014Co-Authors: Shaojun Yang, Yi Hua Jan, Vladimir Mishin, Diane E. Heck, Debra L. Laskin, Jason R. Richardson, Muhammad M. Hossain, Ned D. Heindel, Jeffrey D. LaskinAbstract:Sepiapterin reductase (SPR) catalyzes the reduction of Sepiapterin to dihydrobiopterin (BH2), the precursor for tetrahydrobiopterin (BH4), a cofactor critical for nitric oxide biosynthesis and alkylglycerol and aromatic amino acid metabolism. SPR also mediates chemical redox cycling, catalyzing one-electron reduction of redox-active chemicals, including quinones and bipyridinium herbicides (e.g., menadione, 9,10-phenanthrenequinone, and diquat); rapid reaction of the reduced radicals with molecular oxygen generates reactive oxygen species (ROS). Using recombinant human SPR, sulfonamide- and sulfonylurea-based sulfa drugs were found to be potent noncompetitive inhibitors of both Sepiapterin reduction and redox cycling. The most potent inhibitors of Sepiapterin reduction (IC50s = 31–180 nM) were sulfasalazine, sulfathiazole, sulfapyridine, sulfamethoxazole, and chlorpropamide. Higher concentrations of the sulfa drugs (IC50s = 0.37–19.4 μM) were required to inhibit redox cycling, presumably because of distinct mechanisms of Sepiapterin reduction and redox cycling. In PC12 cells, which generate catecholamine and monoamine neurotransmitters via BH4-dependent amino acid hydroxylases, sulfa drugs inhibited both BH2/BH4 biosynthesis and redox cycling mediated by SPR. Inhibition of BH2/BH4 resulted in decreased production of dopamine and dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 5-hydroxytryptamine. Sulfathiazole (200 μM) markedly suppressed neurotransmitter production, an effect reversed by BH4. These data suggest that SPR and BH4-dependent enzymes, are “off-targets” of sulfa drugs, which may underlie their untoward effects. The ability of the sulfa drugs to inhibit redox cycling may ameliorate ROS-mediated toxicity generated by redox active drugs and chemicals, contributing to their anti-inflammatory activity.
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Sulfa Drugs Inhibit Sepiapterin Reduction and Chemical Redox Cycling by Sepiapterin Reductase
2014Co-Authors: Shaojun Yang, Yi Hua Jan, Vladimir Mishin, Diane E. Heck, Debra L. Laskin, Jason R. Richardson, Muhammad M. Hossain, Ned D. Heindel, Jeffrey D. LaskinAbstract:Sepiapterin reductase (SPR) catalyzes the reduction of Sepiapterin to dihydrobiopterin (BH2), the precursor for tetrahydrobiopterin (BH4), a cofactor critical for nitric oxide biosynthesis and alkylglycerol and aromatic amino acid metabolism. SPR also medi-ates chemical redox cycling, catalyzing one-electron reduction of redox-active chemicals, including quinones and bipyridinium herbicides (e.g., menadione, 9,10-phenanthrenequinone, and di-quat); rapid reaction of the reduced radicals with molecular oxygen generates reactive oxygen species (ROS). Using recombinant human SPR, sulfonamide- and sulfonylurea-based sulfa drugs were found to be potent noncompetitive inhibitors of both Sepiapterin reduction and redox cycling. Themost potent inhibitors of Sepiapterin reduction (IC50s 5 31–180 nM) were sulfasalazine, sulfathiazole, sulfapyridine, sulfamethoxazole, and chlorpropamide. Higher con
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Sepiapterin Reductase Mediates Chemical Redox Cycling in Lung Epithelial Cells
The Journal of biological chemistry, 2013Co-Authors: Shaojun Yang, Yi Hua Jan, Joshua P. Gray, Vladimir Mishin, Diane E. Heck, Debra L. Laskin, Jeffrey D. LaskinAbstract:Abstract In the lung, chemical redox cycling generates highly toxic reactive oxygen species that can cause alveolar inflammation and damage to the epithelium, as well as fibrosis. In this study, we identified a cytosolic NADPH-dependent redox cycling activity in mouse lung epithelial cells as Sepiapterin reductase (SPR), an enzyme important for the biosynthesis of tetrahydrobiopterin. Human SPR was cloned and characterized. In addition to reducing Sepiapterin, SPR mediated chemical redox cycling of bipyridinium herbicides and various quinones; this activity was greatest for 1,2-naphthoquinone followed by 9,10-phenanthrenequinone, 1,4-naphthoquinone, menadione, and 2,3-dimethyl-1,4-naphthoquinone. Whereas redox cycling chemicals inhibited Sepiapterin reduction, Sepiapterin had no effect on redox cycling. Additionally, inhibitors such as dicoumarol, N-acetylserotonin, and indomethacin blocked Sepiapterin reduction, with no effect on redox cycling. Non-redox cycling quinones, including benzoquinone and phenylquinone, were competitive inhibitors of Sepiapterin reduction but noncompetitive redox cycling inhibitors. Site-directed mutagenesis of the SPR C-terminal substrate-binding site (D257H) completely inhibited Sepiapterin reduction but had minimal effects on redox cycling. These data indicate that SPR-mediated reduction of Sepiapterin and redox cycling occur by distinct mechanisms. The identification of SPR as a key enzyme mediating chemical redox cycling suggests that it may be important in generating cytotoxic reactive oxygen species in the lung. This activity, together with inhibition of Sepiapterin reduction by redox-active chemicals and consequent deficiencies in tetrahydrobiopterin, may contribute to tissue injury.
Meixiao Zhan - One of the best experts on this subject based on the ideXlab platform.
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Sepiapterin reductase: Characteristics and role in diseases.
Journal of cellular and molecular medicine, 2020Co-Authors: Peng Chen, Li Sun, Shengtao Yuan, Zujue Cheng, Meixiao ZhanAbstract:Sepiapterin reductase, a homodimer composed of two subunits, plays an important role in the biosynthesis of tetrahydrobiopterin. Furthermore, Sepiapterin reductase exhibits a wide distribution in different tissues and is associated with many diseases, including brain dysfunction, chronic pain, cardiovascular disease and cancer. With regard to drugs targeting Sepiapterin reductase, many compounds have been identified and provide potential methods to treat various diseases. However, the underlying mechanism of Sepiapterin reductase in many biological processes is unclear. Therefore, this article summarized the structure, distribution and function of Sepiapterin reductase, as well as the relationship between Sepiapterin reductase and different diseases, with the aim of finding evidence to guide further studies on the molecular mechanisms and the potential clinical value of Sepiapterin reductase. In particular, the different effects induced by the depletion of Sepiapterin reductase or the inhibition of the enzyme suggest that the non-enzymatic activity of Sepiapterin reductase could function in certain biological processes, which also provides a possible direction for Sepiapterin reductase research.
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Sepiapterin reductase promotes hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner.
Cell death & disease, 2020Co-Authors: Meixiao Zhan, Peng Chen, Hongxv Wang, Xinyi Liu, Xingxv Huang, Dezheng PengAbstract:Sepiapterin reductase plays an enzymatic role in the biosynthesis of tetrahydrobiopterin, which is reported in limited studies to regulate the progression of several tumors. However, the role of Sepiapterin reductase in hepatocellular carcinoma remains largely unknown. Here, we found that Sepiapterin reductase was frequently highly expressed in human hepatocellular carcinoma, which was significantly associated with higher T stage, higher tumor node metastasis stage, and even shorter survival of hepatocellular carcinoma patients. Furthermore, cell and animal experiments showed that Sepiapterin reductase depletion inhibited cancer cell proliferation and promoted cancer cell apoptosis. Importantly, the results suggested that Sepiapterin reductase enzymatic activity was not necessary for the progression of hepatocellular carcinoma, based on the comparison between SMMC-7721 and SMMC-7721 containing Sepiapterin reductase mutant. Moreover, we showed that Sepiapterin reductase regulated the development of hepatocellular carcinoma via the FoxO3a/Bim-signaling pathway. Collectively, our study suggests that Sepiapterin reductase controls hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner, which provides a potential prognostic factor and therapeutic strategy for hepatocellular carcinoma.
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Sepiapterin reductase promotes hepatocellular carcinoma progression via foxo3a bim signaling in a nonenzymatic manner
Cell Death and Disease, 2020Co-Authors: Meixiao Zhan, Peng Chen, Li Sun, Shengtao Yuan, Hongxv Wang, Xinyi Liu, Xingxv Huang, Dezheng Peng, Jian DingAbstract:Sepiapterin reductase plays an enzymatic role in the biosynthesis of tetrahydrobiopterin, which is reported in limited studies to regulate the progression of several tumors. However, the role of Sepiapterin reductase in hepatocellular carcinoma remains largely unknown. Here, we found that Sepiapterin reductase was frequently highly expressed in human hepatocellular carcinoma, which was significantly associated with higher T stage, higher tumor node metastasis stage, and even shorter survival of hepatocellular carcinoma patients. Furthermore, cell and animal experiments showed that Sepiapterin reductase depletion inhibited cancer cell proliferation and promoted cancer cell apoptosis. Importantly, the results suggested that Sepiapterin reductase enzymatic activity was not necessary for the progression of hepatocellular carcinoma, based on the comparison between SMMC-7721 and SMMC-7721 containing Sepiapterin reductase mutant. Moreover, we showed that Sepiapterin reductase regulated the development of hepatocellular carcinoma via the FoxO3a/Bim-signaling pathway. Collectively, our study suggests that Sepiapterin reductase controls hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner, which provides a potential prognostic factor and therapeutic strategy for hepatocellular carcinoma.
Jian Ding - One of the best experts on this subject based on the ideXlab platform.
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Sepiapterin reductase promotes hepatocellular carcinoma progression via foxo3a bim signaling in a nonenzymatic manner
Cell Death and Disease, 2020Co-Authors: Meixiao Zhan, Peng Chen, Li Sun, Shengtao Yuan, Hongxv Wang, Xinyi Liu, Xingxv Huang, Dezheng Peng, Jian DingAbstract:Sepiapterin reductase plays an enzymatic role in the biosynthesis of tetrahydrobiopterin, which is reported in limited studies to regulate the progression of several tumors. However, the role of Sepiapterin reductase in hepatocellular carcinoma remains largely unknown. Here, we found that Sepiapterin reductase was frequently highly expressed in human hepatocellular carcinoma, which was significantly associated with higher T stage, higher tumor node metastasis stage, and even shorter survival of hepatocellular carcinoma patients. Furthermore, cell and animal experiments showed that Sepiapterin reductase depletion inhibited cancer cell proliferation and promoted cancer cell apoptosis. Importantly, the results suggested that Sepiapterin reductase enzymatic activity was not necessary for the progression of hepatocellular carcinoma, based on the comparison between SMMC-7721 and SMMC-7721 containing Sepiapterin reductase mutant. Moreover, we showed that Sepiapterin reductase regulated the development of hepatocellular carcinoma via the FoxO3a/Bim-signaling pathway. Collectively, our study suggests that Sepiapterin reductase controls hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner, which provides a potential prognostic factor and therapeutic strategy for hepatocellular carcinoma.
Peng Chen - One of the best experts on this subject based on the ideXlab platform.
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Sepiapterin reductase: Characteristics and role in diseases.
Journal of cellular and molecular medicine, 2020Co-Authors: Peng Chen, Li Sun, Shengtao Yuan, Zujue Cheng, Meixiao ZhanAbstract:Sepiapterin reductase, a homodimer composed of two subunits, plays an important role in the biosynthesis of tetrahydrobiopterin. Furthermore, Sepiapterin reductase exhibits a wide distribution in different tissues and is associated with many diseases, including brain dysfunction, chronic pain, cardiovascular disease and cancer. With regard to drugs targeting Sepiapterin reductase, many compounds have been identified and provide potential methods to treat various diseases. However, the underlying mechanism of Sepiapterin reductase in many biological processes is unclear. Therefore, this article summarized the structure, distribution and function of Sepiapterin reductase, as well as the relationship between Sepiapterin reductase and different diseases, with the aim of finding evidence to guide further studies on the molecular mechanisms and the potential clinical value of Sepiapterin reductase. In particular, the different effects induced by the depletion of Sepiapterin reductase or the inhibition of the enzyme suggest that the non-enzymatic activity of Sepiapterin reductase could function in certain biological processes, which also provides a possible direction for Sepiapterin reductase research.
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Sepiapterin reductase promotes hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner.
Cell death & disease, 2020Co-Authors: Meixiao Zhan, Peng Chen, Hongxv Wang, Xinyi Liu, Xingxv Huang, Dezheng PengAbstract:Sepiapterin reductase plays an enzymatic role in the biosynthesis of tetrahydrobiopterin, which is reported in limited studies to regulate the progression of several tumors. However, the role of Sepiapterin reductase in hepatocellular carcinoma remains largely unknown. Here, we found that Sepiapterin reductase was frequently highly expressed in human hepatocellular carcinoma, which was significantly associated with higher T stage, higher tumor node metastasis stage, and even shorter survival of hepatocellular carcinoma patients. Furthermore, cell and animal experiments showed that Sepiapterin reductase depletion inhibited cancer cell proliferation and promoted cancer cell apoptosis. Importantly, the results suggested that Sepiapterin reductase enzymatic activity was not necessary for the progression of hepatocellular carcinoma, based on the comparison between SMMC-7721 and SMMC-7721 containing Sepiapterin reductase mutant. Moreover, we showed that Sepiapterin reductase regulated the development of hepatocellular carcinoma via the FoxO3a/Bim-signaling pathway. Collectively, our study suggests that Sepiapterin reductase controls hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner, which provides a potential prognostic factor and therapeutic strategy for hepatocellular carcinoma.
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Sepiapterin reductase promotes hepatocellular carcinoma progression via foxo3a bim signaling in a nonenzymatic manner
Cell Death and Disease, 2020Co-Authors: Meixiao Zhan, Peng Chen, Li Sun, Shengtao Yuan, Hongxv Wang, Xinyi Liu, Xingxv Huang, Dezheng Peng, Jian DingAbstract:Sepiapterin reductase plays an enzymatic role in the biosynthesis of tetrahydrobiopterin, which is reported in limited studies to regulate the progression of several tumors. However, the role of Sepiapterin reductase in hepatocellular carcinoma remains largely unknown. Here, we found that Sepiapterin reductase was frequently highly expressed in human hepatocellular carcinoma, which was significantly associated with higher T stage, higher tumor node metastasis stage, and even shorter survival of hepatocellular carcinoma patients. Furthermore, cell and animal experiments showed that Sepiapterin reductase depletion inhibited cancer cell proliferation and promoted cancer cell apoptosis. Importantly, the results suggested that Sepiapterin reductase enzymatic activity was not necessary for the progression of hepatocellular carcinoma, based on the comparison between SMMC-7721 and SMMC-7721 containing Sepiapterin reductase mutant. Moreover, we showed that Sepiapterin reductase regulated the development of hepatocellular carcinoma via the FoxO3a/Bim-signaling pathway. Collectively, our study suggests that Sepiapterin reductase controls hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner, which provides a potential prognostic factor and therapeutic strategy for hepatocellular carcinoma.
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Sepiapterin reductase regulation of endothelial tetrahydrobiopterin and nitric oxide bioavailability.
American journal of physiology. Heart and circulatory physiology, 2009Co-Authors: Ling Gao, Peng Chen, Yuh Fen Pung, Jun Zhang, Ting Wang, Miguel Meza, Ligia Toro, Hua CaiAbstract:Sepiapterin reductase (SPR) catalyzes the final step of tetrahydrobiopterin (H4B) biosynthesis and the first step of H4B regeneration from an exogenous precursor Sepiapterin. Despite the potential ...
