172 results match your criteria srx

Hyperoxidation of Peroxiredoxins and Effects on Physiology of .

Antioxidants (Basel) 2021 Apr 15;10(4). Epub 2021 Apr 15.

Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USA.

The catalytic activity of peroxiredoxins (Prx) is determined by the conserved peroxidatic cysteine (Cys), which reacts with peroxides to form sulfenic acid (Cys-SOH). Under conditions of oxidative stress, Cys is oxidized to catalytically inactive sulfinic (Cys-SO) and sulfonic (Cys-SO) forms. The Cys-SO form can be reduced in a reaction catalyzed by sulfiredoxin (Srx). Read More

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Maturation of Mitochondrially Targeted Prx V Involves a Second Cleavage by Mitochondrial Intermediate Peptidase That Is Sensitive to Inhibition by HO.

Antioxidants (Basel) 2021 Feb 25;10(3). Epub 2021 Feb 25.

Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea.

Prx V mRNA contains two in-frame AUG codons, producing a long (L-Prx V) and short form of Prx V (S-Prx V), and mouse L-Prx V is expressed as a precursor protein containing a 49-amino acid N-terminal mitochondria targeting sequence. Here, we show that the N-terminal 41-residue sequence of L-Prx V is cleaved by mitochondrial processing peptidase (MPP) in the mitochondrial matrix to produce an intermediate Prx V (I-Prx V) with a destabilizing phenylalanine at its N-terminus, and further, that the next 8-residue sequence is cleaved by mitochondrial intermediate peptidase (MIP) to convert I-Prx V to a stabilized mature form that is identical to S-Prx V. Further, we show that when mitochondrial HO levels are increased in HeLa cells using rotenone, in several mouse tissues by deleting Prx III, and in the adrenal gland by deleting Srx or by exposing mice to immobilized stress, I-Prx V accumulates transiently and mature S-Prx V levels decrease in mitochondria over time. Read More

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February 2021

Sirtuin 6 (SIRT6) regulates redox homeostasis and signaling events in human articular chondrocytes.

Free Radic Biol Med 2021 Apr 16;166:90-103. Epub 2021 Feb 16.

Division of Rheumatology, Allergy and Immunology and the Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address:

The nuclear localized protein deacetylase, SIRT6, has been identified as a crucial regulator of biological processes that drive aging. Among these processes, SIRT6 can promote resistance to oxidative stress conditions, but the precise mechanisms remain unclear. The objectives of this study were to examine the regulation of SIRT6 activity by age and oxidative stress and define the role of SIRT6 in maintaining redox homeostasis in articular chondrocytes. Read More

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Cardiac myosin super relaxation (SRX): a perspective on fundamental biology, human disease and therapeutics.

Biol Open 2021 Feb 15;10(2). Epub 2021 Feb 15.

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK

The fundamental basis of muscle contraction 'the sliding filament model' (Huxley and Niedergerke, 1954; Huxley and Hanson, 1954) and the 'swinging, tilting crossbridge-sliding filament mechanism' (Huxley, 1969; Huxley and Brown, 1967) nucleated a field of research that has unearthed the complex and fascinating role of myosin structure in the regulation of contraction. A recently discovered energy conserving state of myosin termed the super relaxed state (SRX) has been observed in filamentous myosins and is central to modulating force production and energy use within the sarcomere. Modulation of myosin function through SRX is a rapidly developing theme in therapeutic development for both cardiovascular disease and infectious disease. Read More

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February 2021

To lie or not to lie: Super-relaxing with myosins.

Elife 2021 Feb 10;10. Epub 2021 Feb 10.

Department of Biochemistry, Stanford University School of Medicine, Stanford, United States.

Since the discovery of muscle in the 19th century, myosins as molecular motors have been extensively studied. However, in the last decade, a new functional super-relaxed (SRX) state of myosin has been discovered, which has a 10-fold slower ATP turnover rate than the already-known non-actin-bound, disordered relaxed (DRX) state. These two states are in dynamic equilibrium under resting muscle conditions and are thought to be significant contributors to adaptive thermogenesis in skeletal muscle and can act as a reserve pool that may be recruited when there is a sustained demand for increased cardiac muscle power. Read More

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February 2021

Clinico-pathological and prognostic implications of Srx, Nrf2, and PROX1 expression in gastric cancer and adjacent non-neoplastic mucosa - an immunohistochemical study.

Contemp Oncol (Pozn) 2020 4;24(4):229-240. Epub 2021 Jan 4.

General Surgery, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Introduction: Sulfiredoxin (Srx), which is an endogenous antioxidant substance which could, regulate the signaling pathways of reactive oxygen species. Nuclear factor erythroid 2-related factor 2 (Nrf2) is Cap-N-collar (CNC) transcription factors family member that have essential roles in regulation of antioxidant response. The transcription factor PROX1 is a transcription factor and a key regulatory protein in cancer development. Read More

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January 2021

The G-Protein-Coupled Receptor SRX-97 Is Required for Concentration-Dependent Sensing of Benzaldehyde in .

eNeuro 2021 Jan-Feb;8(1). Epub 2021 Jan 28.

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Punjab 140306, India

The G-protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs) in the olfactory system function to sense the surrounding environment and respond to various odorants. The genes coding for olfactory receptors in are larger in number in comparison to those in mammals, suggesting complexity in the receptor-odorant relationships. Recent studies have shown that the same odorant in different concentrations could act on multiple receptors in different neurons to induce attractive or repulsive responses. Read More

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January 2021

The role of the super-relaxed state of myosin in human metabolism.

Metabol Open 2021 Mar 23;9:100068. Epub 2020 Nov 23.

Department of Biochemistry and Biophysics, University of California, San Francisco, CA, 94143, USA.

Background: The super-relaxed state of myosin (SRX) plays a fundamental role in maintaining the low resting metabolic rate of skeletal muscle. Our previous work on this state has been in animal models. Piperine is a small molecule that has been shown to destabilize the SRX in rabbit fast twitch fibers. Read More

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Making waves: A proposed new role for myosin-binding protein C in regulating oscillatory contractions in vertebrate striated muscle.

J Gen Physiol 2021 Mar;153(3)

Myosin-binding protein C (MyBP-C) is a critical regulator of muscle performance that was first identified through its strong binding interactions with myosin, the force-generating protein of muscle. Almost simultaneously with its discovery, MyBP-C was soon found to bind to actin, the physiological catalyst for myosin's activity. However, the two observations posed an apparent paradox, in part because interactions of MyBP-C with myosin were on the thick filament, whereas MyBP-C interactions with actin were on the thin filament. Read More

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Synthetic thick filaments: A new avenue for better understanding the myosin super-relaxed state in healthy, diseased, and mavacamten-treated cardiac systems.

J Biol Chem 2020 Dec 3;296:100114. Epub 2020 Dec 3.

Department of Biology, MyoKardia, Inc., Brisbane, California, USA. Electronic address:

A hallmark feature of myosin-II is that it can spontaneously self-assemble into bipolar synthetic thick filaments (STFs) in low-ionic-strength buffers, thereby serving as a reconstituted in vitro model for muscle thick filaments. Although these STFs have been extensively used for structural characterization, their functional evaluation has been limited. In this report, we show that myosins in STFs mirror the more electrostatic and cooperative interactions that underlie the energy-sparing super-relaxed (SRX) state, which are not seen using shorter myosin subfragments, heavy meromyosin (HMM) and myosin subfragment 1 (S1). Read More

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December 2020

Super-relaxed state of myosin in human skeletal muscle is fiber-type dependent.

Am J Physiol Cell Physiol 2020 12 30;319(6):C1158-C1162. Epub 2020 Sep 30.

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota.

The myosin super-relaxed state (SRX) in skeletal muscle is hypothesized to play an important role in regulating muscle contractility and thermogenesis in humans but has only been examined in model organisms. Here we report the first human skeletal muscle SRX measurements, using quantitative epifluorescence microscopy of fluorescent 2'/3'--(-methylanthraniloyl) ATP (mantATP) single-nucleotide turnover. Myosin heavy chain (MHC) isoform expression was determined using gel electrophoresis for each permeabilized vastus lateralis fiber, to allow for novel comparisons of SRX between fiber types. Read More

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December 2020

Static Softening Behavior and Modified Kinetics of Al 2219 Alloy Based on a Double-Pass Hot Compression Test.

Materials (Basel) 2020 Sep 1;13(17). Epub 2020 Sep 1.

Light Alloy Research Institute, Central South University, Changsha 410083, China.

In this paper, the static softening mechanism of a 2219 aluminum alloy was studied based on a double-pass isothermal compression test. For the experiment, different temperatures (623 K, 723 K, and 773 K), strain rates (0.1/s, 1/s, and 10/s), deformation ratios (20%, 30%, and 40%), and insulation periods (5 s, 30 s, and 60 s) were used. Read More

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September 2020

Imaging ATP Consumption in Resting Skeletal Muscle: One Molecule at a Time.

Biophys J 2020 09 15;119(6):1050-1055. Epub 2020 Aug 15.

Department of Molecular Physiology and Biophysics, Larner College of Medicine, Burlington, Vermont. Electronic address:

Striated muscle contraction is the result of sarcomeres, the basic contractile unit, shortening because of hydrolysis of adenosine triphosphate (ATP) by myosin molecular motors. In noncontracting, "relaxed" muscle, myosin still hydrolyzes ATP slowly, contributing to the muscle's overall resting metabolic rate. Furthermore, when relaxed, myosin partition into two kinetically distinct subpopulations: a faster-hydrolyzing "relaxed" population, and a slower-hydrolyzing "super relaxed" (SRX) population. Read More

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September 2020

The Myosin SRX Comes into Focus.

Joseph M Muretta

Biophys J 2020 09 15;119(6):1041-1042. Epub 2020 Aug 15.

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota. Electronic address:

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September 2020

A syndrome-based approach to antimicrobial stewardship in an Arizona skilled nursing facility-Moving the needle through quality improvement.

Am J Infect Control 2020 12 4;48(12):1537-1539. Epub 2020 Aug 4.

Sagewood Acacia Health Center, Phoenix, AZ.

In 2015, an Arizona skilled nursing facility implemented an antibiotic stewardship protocol targeting unnecessary prescribing for suspect urinary tract infection. The protocol emphasized auditing of culturing and prescribing practices, feedback to prescribers, engagement of clinical staff, and educational in-services. Between Quarter 4 of 2014 (baseline) and Quarter 1 of 2017, urine culturing, days of antibiotic therapy for suspect urinary tract infection, and Clostridiodes difficile infections per 1,000 resident-days decreased by >50% with no urosepsis events. Read More

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December 2020

Enterotoxin Induces Sulfiredoxin-1 Expression in Intestinal Epithelial Cell Lines Through a Mitogen-Activated Protein Kinases- and Nrf2-Dependent Pathway, Leading to the Suppression of Apoptosis.

Int J Mol Sci 2020 Jul 29;21(15). Epub 2020 Jul 29.

Department of Microbiology, Hanyang University College of Medicine, Seoul 04763, Korea.

Enterotoxigenic is a causative agent of colitis and secrets enterotoxin (BFT), leading to the disease. Sulfiredoxin (Srx)-1 serves to protect from oxidative damages. Although BFT can generate reactive oxygen species in intestinal epithelial cells (IECs), no Srx-1 expression has been reported in ETBF infection. Read More

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Effect of different temperatures to remove reduction gas on the photoluminescence properties of Eu-doped Li (Ba Sr )SiO phosphors.

Luminescence 2021 Feb 15;36(1):20-27. Epub 2020 Jul 15.

Institute of Microelectronics, Department of Electrical Engineering, National Cheng Kung University, Tainan City, Taiwan.

In this study, Eu-doped Li (Ba Sr )SiO powders (x = 0, 0.2, 0.4, and 0. Read More

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February 2021

A study of matrix and admixture elements in fluorine-rich ionic conductors by pulsed glow discharge mass spectrometry.

Rapid Commun Mass Spectrom 2020 Jun;34(11):e8786

Institute of Chemistry, St Petersburg State University, 199034, St Petersburg, Universitetskaya nab. 7/9, Russia.

Rationale: Dopants in ionic conductors play a crucial role in achieving the required electrochemical properties. A slight variation in their concentration considerably affects the conductivity of crystals and their applicability as ionic conductors and laser materials. To ensure the growth of high-quality fluoride crystals, adequate approaches for the quantification of matrix and admixture/dopant components are required. Read More

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Controlled Growth of Sr Ba Nb O Hopper- and Cube-Shaped Nanostructures by Hydrothermal Synthesis.

Chemistry 2020 Jul 30;26(42):9348-9355. Epub 2020 Apr 30.

Department of Materials Science and Engineering, NTNU Norwegian University of Science and Technology, Sem Saelands vei 12, 7491, Trondheim, Norway.

Controlling the shape and size of nanostructured materials has been a topic of interest in the field of material science for decades. In this work, the ferroelectric material Sr Ba Nb O (x=0.32-0. Read More

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Ablation of the N terminus of cardiac essential light chain promotes the super-relaxed state of myosin and counteracts hypercontractility in hypertrophic cardiomyopathy mutant mice.

FEBS J 2020 09 25;287(18):3989-4004. Epub 2020 Feb 25.

Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, FL, USA.

In this study, we focus on the molecular mechanisms associated with the A57G (Ala57-to-Gly57) mutation in myosin essential light chains (ELCs), found to cause hypertrophic cardiomyopathy (HCM) in humans and in mice. Specifically, we studied the effects of A57G on the super-relaxed (SRX) state of myosin that may contribute to the hypercontractile cross-bridge behavior and ultimately lead to pathological cardiac remodeling in transgenic Tg-A57G mice. The disease model was compared to Tg-WT mice, expressing the wild-type human ventricular ELC, and analyzed against Tg-Δ43 mice, expressing the N-terminally truncated ELC, whose hearts hypertrophy with time but do not show any abnormalities in cardiac morphology or function. Read More

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September 2020

Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy.

Circulation 2020 03 27;141(10):828-842. Epub 2020 Jan 27.

Department of Genetics, Harvard Medical School, Boston, MA (C.N.T., A.C.G., G.V., H.W., G.R., A.S., R.A., A.C.P., J.G.S., C.E.S.).

Background: Hypertrophic cardiomyopathy (HCM) is caused by pathogenic variants in sarcomere protein genes that evoke hypercontractility, poor relaxation, and increased energy consumption by the heart and increased patient risks for arrhythmias and heart failure. Recent studies show that pathogenic missense variants in myosin, the molecular motor of the sarcomere, are clustered in residues that participate in dynamic conformational states of sarcomere proteins. We hypothesized that these conformations are essential to adapt contractile output for energy conservation and that pathophysiology of HCM results from destabilization of these conformations. Read More

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Electrodeposition of Sr-substituted hydroxyapatite on low modulus beta-type Ti-45Nb and effect on in vitro Sr release and cell response.

Mater Sci Eng C Mater Biol Appl 2020 Mar 14;108:110425. Epub 2019 Nov 14.

Technische Universität Dresden (TU Dresden), Faculty of Medicine and University Hospital, Centre for Translational Bone, Joint and Soft Tissue Research, Fetscherstr. 74, 01307 Dresden, Germany.

Beta-type Ti-based alloys are promising new materials for bone implants owing to their excellent mechanical biofunctionality and biocompatibility. For treatment of fractures in case of systemic diseases like osteoporosis the generation of implant surfaces which actively support the problematic bone healing is a most important aspect. This work aimed at developing suitable approaches for electrodeposition of Sr-substituted hydroxyapatite (Srx-HAp) coatings onto Ti-45Nb. Read More

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Improving LED Efficiency with the New Polymorph β-Ca Sr AlSiN :Eu.

Chemistry 2020 Jan 14;26(4):795-798. Epub 2020 Jan 14.

OS Phosphors, OSRAM Opto Semiconductors GmbH, Mittelstetter Weg 2, 86830, Schwabmünchen, Germany.

Innovative materials for phosphor-converted white light-emitting diodes (pc-LEDs) are much sought after due to the huge potential of the LED technology to reduce energy consumption worldwide. One of the main levers for further improvements are the conversion phosphors. The system Ca Sr AlSiN :Eu currently provides one of the most important red-emitting phosphors for pc-LEDs. Read More

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January 2020

The crystal structure of sulfiredoxin from Arabidopsis thaliana revealed a more robust antioxidant mechanism in plants.

Biochem Biophys Res Commun 2019 12 8;520(2):347-352. Epub 2019 Oct 8.

School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China; Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui, 230601, China; Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, 230601, China. Electronic address:

Typical 2-cysteine peroxiredoxins (2-Cys Prxs) are critical peroxidase sensors and could be deactivated by the hyperoxidation under oxidative stress. In plants, 2-Cys Prxs present at a high level in chloroplasts and are repaired by Sulfiredoxin. Whereas many studies have explored the mechanism of Sulfiredoxin from Homo sapiens (HsSrx), the molecular mechanism of Sulfiredoxin in plants with unique photosynthesis remains unclear. Read More

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December 2019

Elucidation of the inhibition mechanism of sulfiredoxin using molecular modeling and development of its inhibitors.

J Mol Graph Model 2019 11 31;92:208-215. Epub 2019 Jul 31.

Department of Bioinformatics, Korea University, 2511 Sejong-ro, Sejong, 30019, Republic of Korea. Electronic address:

When intracellular reactive oxygen species (ROS) increase, cancer cells are more vulnerable to oxidative stress compared to normal cells; thus, the collapse of redox homeostasis can lead to selective death of cancer cells. Indeed, recent studies have shown that inhibition of sulfiredoxin (Srx), which participates in antioxidant mechanisms, induces ROS-mediated cancer cell death. In this paper, we describe how an Srx inhibitor, J14 (4-[[[4-[4-(2-chlor-ophenyl)-1-piperazinyl]-6-phenyl-2-pyrimidinyl]thio]methyl]-benzoic acid), interferes with the antioxidant activity of Srx at the molecular level. Read More

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November 2019

Challenges in the use of zinc and its alloys as biodegradable metals: Perspective from biomechanical compatibility.

Acta Biomater 2019 10 23;97:23-45. Epub 2019 Jul 23.

Department of Materials Science and Engineering, Faculty of Engineering, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555, Japan.

To date, more than fifty articles have been published on the feasibility studies of zinc and its alloys as biodegradable metals. These preliminary in vitro and in vivo studies showed acceptable biodegradability and reasonable biocompatibility in bone and blood microenvironments for the experimental Zn-based biodegradable metals and, for some alloy systems, superior mechanical performance over Mg-based biodegradable metals. For instance, the Zn-Li alloys exhibited higher UTS (UTS), and the Zn-Mn alloys exhibited higher elongation (more than 100%). Read More

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October 2019

Frugoside Induces Mitochondria-Mediated Apoptotic Cell Death through Inhibition of Sulfiredoxin Expression in Melanoma Cells.

Cancers (Basel) 2019 Jun 19;11(6). Epub 2019 Jun 19.

Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.

Malignant melanoma is the most life-threatening neoplasm of the skin. Despite the increase in incidence, melanoma is becoming more resistant to current therapeutic agents. The bioactive compound frugoside has been recently reported to inhibit growth when used in various cancer cells. Read More

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Cardiac myosin binding protein-C phosphorylation regulates the super-relaxed state of myosin.

Proc Natl Acad Sci U S A 2019 06 29;116(24):11731-11736. Epub 2019 May 29.

Heart, Lung and Vascular Institute, Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati, Cincinnati, OH 45267

Phosphorylation of cardiac myosin binding protein-C (cMyBP-C) accelerates cardiac contractility. However, the mechanisms by which cMyBP-C phosphorylation increases contractile kinetics have not been fully elucidated. In this study, we tested the hypothesis that phosphorylation of cMyBP-C releases myosin heads from the inhibited super-relaxed state (SRX), thereby determining the fraction of myosin available for contraction. Read More

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A Robust Model for Circadian Redox Oscillations.

Int J Mol Sci 2019 May 13;20(9). Epub 2019 May 13.

Institute for Theoretical Biology, Charité and Humboldt-Universität zu Berlin, 10115 Berlin, Germany.

The circadian clock is an endogenous oscillator that controls daily rhythms in metabolism, physiology, and behavior. Although the timekeeping components differ among species, a common design principle is a transcription-translation negative feedback loop. However, it is becoming clear that other mechanisms can contribute to the generation of 24 h rhythms. Read More

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The redox regulator sulfiredoxin forms a complex with thioredoxin domain-containing 5 protein in response to ER stress in lung cancer cells.

J Biol Chem 2019 05 18;294(22):8991-9006. Epub 2019 Apr 18.

From the Department of Toxicology and Cancer Biology and

Sulfiredoxin (Srx) reduces hyperoxidized 2-cysteine-containing peroxiredoxins (Prxs) and protects cells against oxidative stress. Previous studies have shown that Srx is highly expressed in primary specimens of lung cancer patients and plays a pivotal role in lung tumorigenesis and cancer progression. However, the oncogenic mechanisms of Srx in cancer are incompletely understood. Read More

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