Article
Biochemistry & Molecular Biology
Esha Sircar, Detcho A. Stoyanovsky, Timothy R. Billiar, Arne Holmgren, Rajib Sengupta
Summary: Intracellular reduced glutathione (GSH) is the most abundant intracellular thiol with concentrations ranging from 1-10 mM, playing a crucial role as a potent cellular antioxidant and denitrosylating agent against redox stress. Our study demonstrates GSH mediated denitrosylation of protein nitrosothiols in HepG2 cells using a unique spin-trapping mechanism and identifies two previously unknown substrates of GSH mediated S-denitrosylation.
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Ajanta Chatterji, Rajib Sengupta
Summary: This article discusses the function of nitric oxide and its potential pathological effects, investigates the current research on cellular S-denitrosylases and their potential applications, and provides a detailed analysis of the importance of maintaining cellular redox homeostasis.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Ajanta Chatterji, Rajib Sengupta
Summary: Nitric oxide is a gasotransmitter molecule that plays various roles in cellular processes. Recent research supports the existence of S-nitrosylated proteins within cells, challenging the controversy over their stability. Evidence suggests that these proteins directly regulate functionality and provide insights into cell signaling.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sicong Wang, Yaoying Lu, Kyra Woods, Giovanna Di Trapani, Kathryn F. Tonissen
Summary: Inhibition of thioredoxin reductase (TrxR) has been found to be an effective therapeutic approach for lymphoma. The combination of thioredoxin (Trx) and glutathione (GSH) systems can induce cell apoptosis and enhance the expression of tumor suppressor genes.
Review
Biochemistry & Molecular Biology
Surupa Chakraborty, Esha Sircar, Camelia Bhattacharyya, Ankita Choudhuri, Akansha Mishra, Sreejita Dutta, Sneha Bhatta, Kumar Sachin, Rajib Sengupta
Summary: S-nitrosylation of proteins, resulting from the reaction between cysteine thiols and nitric oxide (NO), is associated with diseases and protein malfunction. It has rapidly emerged as a major cause of various metabolic, respiratory, and cardiac disorders, particularly cancer and neurodegeneration. The field of redox biochemistry has explored other covalently modified versions of proteins, but the S-nitrosoproteome, which refers to the diverse and dynamic repertoire of S-nitrosylated proteins, remains relatively unexplored. Research in this area is uncovering the clinical importance of S-nitrosylation in disease etiology and providing new avenues for prompt diagnosis.
Article
Cardiac & Cardiovascular Systems
Xin Tang, Shuang Zhao, Jieqiong Liu, Xiameng Liu, Xinqi Sha, Changgao Huang, Lulu Hu, Shixiu Sun, Yuanqing Gao, Hongshan Chen, Zhiren Zhang, Dongjin Wang, Yuexi Gu, Shaoliang Chen, Liansheng Wang, Aihua Gu, Feng Chen, Jun Pu, Xin Chen, Bo Yu, Liping Xie, Zhengrong Huang, Yi Han, Yong Ji
Summary: This study identified a novel species of GSNOR localized in mitochondria and found that mitochondrial GSNOR plays a crucial role in maintaining mitochondrial homeostasis through ANT1 denitrosylation, providing a potential novel therapeutic target for heart failure.
CIRCULATION RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Rajib Sengupta, Lucia Coppo, Esha Sircar, Pradeep Mishra, Arne Holmgren
Summary: The S-nitrosylation of the R1 subunit inhibits RNR catalysis, while denitrosylation or an externally supplied peptide containing vicinal dithiols can restore enzyme activity. The Trx system is necessary for regeneration of oxidized vicinal dithiols in the C-terminal tail/peptide, highlighting the importance of C-terminal vicinal dithiols in regenerating the RNR activity of S-nitrosylated R1 subunits.
Article
Oncology
Dana M. Zaher, Wafaa S. Ramadan, Raafat El-Awady, Hany A. Omar, Fatema Hersi, Vunnam Srinivasulu, Ibrahim Y. Hachim, Farah I. Al-Marzooq, Cijo G. Vazhappilly, Salim Merali, Carmen Merali, Nelson C. Soares, Paul Schilf, Saleh M. Ibrahim, Taleb H. Al-Tel
Summary: SIMR1281 displayed a multi-target anticancer effect by dual inhibition of glutathione and thioredoxin reductases, inhibiting cell proliferation and inducing apoptosis by inducing DNA damage, perturbing the cell cycle, and pathway inactivation.
Article
Multidisciplinary Sciences
Omer F. Bay, Kelly S. Hayes, Jean-Marc Schwartz, Richard K. Grencis, Ian S. Roberts
Summary: Genome-scale metabolic model of Trichuris muris reveals the essential role of Thioredoxin Reductase (TrxR) enzyme for its survival, as well as the mechanism of glutathione reduction by TrxR enzyme. The model also predicts several essential amino acids that cannot be synthesized by T. muris.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Elizabeth Corteselli, Reem Aboushousha, Yvonne Janssen-Heininger
Summary: Glutathione plays a crucial role as an antioxidant and regulates biological processes through protein S-glutathionylation. Recent studies have implicated protein S-glutathionylation in the pathogenesis of various diseases, including idiopathic pulmonary fibrosis, and its association with oxidative stress and epithelial cell apoptosis.
Article
Biochemistry & Molecular Biology
Patricia P. Adriani, Fernanda C. R. de Paiva, Gabriel S. de Oliveira, Amanda C. Leite, Adriana S. Sanches, Adriana Rios Lopes, Marcio V. B. Dias, Felipe S. Chambergo
Summary: The study characterized the functional and structural features of a glutathione peroxidase (GPx) identified in Trichoderma reesei, demonstrating that TrGPx is a thioredoxin peroxidase with better hydrolysis activity towards H2O2 than t-BOOH. Additionally, TrGPx showed optimal pH range and half-life at 80 degrees Celsius.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Debaprasad Koner, Niharika Nag, Parismita Kalita, Aditya K. Padhi, Timir Tripathi, Nirmalendu Saha
Summary: The presence of thioredoxin glutathione reductase (TGR) in the facultative air-breathing catfish, Clarias magur, was identified for the first time. The TGR enzyme showed both TrxR and GR activities, contributing to the maintenance of redox homeostasis and antioxidant defense under oxidative stress induced by environmental stressors. Phylogenetic analysis revealed its relationship to fish TrxRs and distant relation to platyhelminth parasites TGRs. The characterization of C. magur TGR provides insights into its unique adaptation to environmental challenges.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Plant Sciences
Madhu, Alok Sharma, Amandeep Kaur, Shivi Tyagi, Santosh Kumar Upadhyay
Summary: This review discusses the importance of glutathione peroxidases (GPXs) in plant physiology, including their role in scavenging reactive oxygen species, maintaining redox homeostasis, and responding to environmental stresses. The study of GPX genes provides valuable information for genetic engineering to enhance agricultural plant yields under unfavorable conditions.
JOURNAL OF PLANT GROWTH REGULATION
(2023)
Article
Biochemistry & Molecular Biology
Warin Rangubpit, Eukote Suwan, Danai Sangthong, Kannika Wongpanit, Roger W. Stich, Prapasiri Pongprayoon, Sathaporn Jittapalapong
Summary: In this study, molecular dynamics simulations were conducted to investigate the binding of GTX and GSH to RmGST. It was found that GSH binds tighter and sits rigidly inside the G-site, while GTX occupies both active sites.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Azahara Casatejada, Leonor Puerto-Galan, Juan M. Perez-Ruiz, Francisco J. Cejudo
Summary: Oxidizing signals mediated by thiol-dependent peroxidase activity play a crucial role in chloroplast redox balance, with both 2-Cys peroxiredoxins (PRXs) and glutathione peroxidases (GPXs) being involved. However, the specific contribution of GPXs in this process is not well understood. This study generated mutant plants devoid of GPXs to investigate their functional relationship with the NADPH-dependent thioredoxin reductase C (NTRC)-2-Cys PRXs redox system. The results indicate that GPXs contribute to chloroplast redox homeostasis independently of NTRC.
Article
Chemistry, Analytical
Xin Zuo, Ying Zhao, Jintao Zhao, Yanfang Ouyang, Wenjun Qian, Yinmei Hou, Chong Yu, Xiaoyuan Ren, Lili Zou, Jianguo Fang, Jun Lu
Summary: This study found that TRFS-green can be used as a probe to measure the overall activities of Trxs and Grxs in bacteria. The contributions of different Trxs and Grxs to cellular redox regulation were clarified using Trx and Grx null mutant strains, and it was found that E.coli Grx2 and Grx3 exhibited higher reducing capability.
Article
Biochemistry & Molecular Biology
Airlla Laana de Medeiros Cavalcanti, Patricia Keytth Lins Rocha, Zhengbing Zhuge, Marcelo F. Montenegro, Luciano Leite Paulo, Leonidas das Gracas Mendes-Junior, Maria Claudia Rodrigues Brandao, Petronio F. Athayde-Filho, Jon O. Lundberg, Eddie Weitsberg, Mattias Carlstrom, Valdir de Andrade Braga
Summary: This study investigates the cardiovascular effects of the new organic nitrate NDIBP, and finds that it has a blood pressure-lowering effect without inducing tolerance. These effects may be mediated through the activation of the NO-sGC-cGMP signaling pathway and positive modulation of K+ channels in vascular smooth muscle.
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Esha Sircar, Detcho A. Stoyanovsky, Timothy R. Billiar, Arne Holmgren, Rajib Sengupta
Summary: Intracellular reduced glutathione (GSH) is the most abundant intracellular thiol with concentrations ranging from 1-10 mM, playing a crucial role as a potent cellular antioxidant and denitrosylating agent against redox stress. Our study demonstrates GSH mediated denitrosylation of protein nitrosothiols in HepG2 cells using a unique spin-trapping mechanism and identifies two previously unknown substrates of GSH mediated S-denitrosylation.
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ying Zhao, Xin Zuo, Shuang Liu, Wenjun Qian, Xuewen Tang, Jun Lu
Summary: The Trx and Grx systems are critical disulfide reductase systems in cell activities, with significant differences between prokaryotes and mammals. Fast-TRFS can be utilized to detect cellular disulfide reducibility in bacteria, where Trx system is shown to be the predominant enzyme for fast disulfide reduction.
Review
Biochemistry & Molecular Biology
Jon O. Lundberg, Eddie Weitzberg
Summary: Nitric oxide (NO) is a key regulator of various physiological processes including cardiovascular function, metabolism, neurotransmission, and immunity. Aberrant NO signaling is a central feature of many major disorders, and novel insights into NO biosynthesis and signal transduction mechanisms are continuously emerging in the field.
Article
Biochemistry & Molecular Biology
Shuang Liu, Xing Wen, Qihan Huang, Minghui Zhu, Jun Lu
Summary: Cisplatin is an effective chemotherapy drug for solid tumors but also causes various side effects, especially nephrotoxicity. Previous studies have shown a correlation between selenoenzymes and cisplatin-induced renal damage. This study established mouse models with different selenium intake levels and found that selenium deficiency increased sensitivity to cisplatin-induced damage, while selenium supplementation protected against renal injury.
Article
Biochemistry & Molecular Biology
Surupa Chakraborty, Prerona Mukherjee, Rajib Sengupta
Summary: Ribonucleotide reductase (RNR) is a crucial enzyme involved in DNA synthesis and repair, with potential implications in cancer development. Recent research has highlighted the significant role of NO in RNR inhibition, aiding in the development of new drugs and therapies.
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Surupa Chakraborty, Esha Sircar, Camelia Bhattacharyya, Ankita Choudhuri, Akansha Mishra, Sreejita Dutta, Sneha Bhatta, Kumar Sachin, Rajib Sengupta
Summary: S-nitrosylation of proteins, resulting from the reaction between cysteine thiols and nitric oxide (NO), is associated with diseases and protein malfunction. It has rapidly emerged as a major cause of various metabolic, respiratory, and cardiac disorders, particularly cancer and neurodegeneration. The field of redox biochemistry has explored other covalently modified versions of proteins, but the S-nitrosoproteome, which refers to the diverse and dynamic repertoire of S-nitrosylated proteins, remains relatively unexplored. Research in this area is uncovering the clinical importance of S-nitrosylation in disease etiology and providing new avenues for prompt diagnosis.
Review
Biochemistry & Molecular Biology
Geir Bjorklund, Lili Zou, Massimiliano Peana, Christos T. Chasapis, Tony Hangan, Jun Lu, Michael Maes
Summary: The thioredoxin system plays a vital role in various neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, through its involvement in oxidative stress, apoptotic, neuro-immune, and pro-survival pathways. Numerous aberrations in the system, influenced by genetic and environmental factors, may contribute to the development of these neuropsychiatric disorders. Targeting the thioredoxin system could be a promising approach for the prevention and treatment of neurodegenerative, neuro-inflammatory, and neuro-oxidative stress processes and related brain disorders.
Editorial Material
Biochemistry & Molecular Biology
Jon O. O. Lundberg
Editorial Material
Endocrinology & Metabolism
Jon O. Lundberg, Tomas Schiffer, Eddie Weitzberg, Filip J. Larsen
Summary: Distance running requires high absolute oxygen consumption, while breath-hold diving prefers the opposite. We compared exercise parameters and mitochondrial function in a competitive triathlete with an accomplished breath-hold diver and observed significant differences, which may explain their success.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Peripheral Vascular Disease
Thomas Willmott, Laura Ormesher, Andrew J. Mcbain, Gavin J. Humphreys, Jenny E. Myers, Gurdeep Singh, Jon O. Lundberg, Eddie Weitzberg, Carina Nihlen, Elizabeth C. Cottrell
Summary: This study aimed to investigate the role of oral microbiota profiles and oral nitrate-reducing capacity in explaining individual differences in blood pressure (BP) lowering following dietary nitrate supplementation. The results showed that women with hypertension had lower salivary nitrite concentrations and reduced abundance of nitrate-reducing bacteria compared to normotensive women. Oral nitrate reductase (NaR) activity did not differ significantly between pregnant and nonpregnant women, but it tended to be lower in hypertensive women. Oral NaR activity was associated with both baseline diastolic BP and changes in diastolic BP after acute nitrate intake.
Letter
Endocrinology & Metabolism
Jon O. Lundberg, Eddie Weitzberg
Summary: Goitre is commonly caused by iodine deficiency in the diet, and in high-altitude areas, the high levels of endogenous inorganic nitrate may further increase the risk of goitre and thyroid dysfunction.
Article
Chemistry, Multidisciplinary
Guotao Peng, Viviana Gonzalez, Ester Vazquez, Jon O. Lundberg, Bengt Fadeel
Summary: This study demonstrates that two-dimensional molybdenum disulfide (MoS2) nanosheets can trigger neutrophil extracellular traps (NETs) and possess antibacterial effects. Additionally, the MoS2 nanosheets exhibit nitrite reductase-like properties.
Article
Medicine, Research & Experimental
Jiangning Yang, Michaela L. Sundqvist, Xiaowei Zheng, Tong Jiao, Aida Collado, Yahor Tratsiakovich, Ali Mahdi, John Tengbom, Evanthia Mergia, Sergiu-Bogdan Catrina, Zhichao Zhou, Mattias Carlstroem, Takaaki Akaike, Miriam M. Cortese-Krott, Eddie Weitzberg, Jon O. Lundberg, John Pernow
Summary: Red blood cells exposed to hypoxia release cGMP, which acts as a cardioprotective mediator by activating cardiomyocyte protein kinase G. Oral administration of nitrate enhances the cardioprotective effect of hypoxic red blood cells.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
