PubMed Central (PMC3 - NLM DTD)
(2.524.416 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
Antioxidants & Redox Signaling
Mostrando recursos 1 - 20 de 401
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NADPH Oxidase 1-Mediated Oxidative Stress Leads to Dopamine Neuron Death in Parkinson's Disease - Choi, Dong-Hee; Cristóvão, Ana Clara; Guhathakurta, Subhrangshu; Lee, Jongmin; Joh, Tong H.; Beal, M. Flint; Kim, Yoon-Seong
Aim: Oxidative stress has long been considered as a major contributing factor in the pathogenesis of Parkinson's disease. However, molecular sources for reactive oxygen species in Parkinson's disease have not been clearly elucidated. Herein, we sought to investigate whether a superoxide-producing NADPH oxidases (NOXs) are implicated in oxidative stress-mediated dopaminergic neuronal degeneration. Results: Expression of various Nox isoforms and cytoplasmic components were investigated in N27, rat dopaminergic cells. While most of Nox isoforms were constitutively expressed, Nox1 expression was significantly increased after treatment with 6-hydroxydopamine. Rac1, a key regulator in the Nox1 system, was also activated. Striatal injection of 6-hydroxydopamine...
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Mitochondrial Regulation of Cell Cycle and Proliferation - Antico Arciuch, Valeria Gabriela; Elguero, María Eugenia; Poderoso, Juan José; Carreras, María Cecilia
Eukaryotic mitochondria resulted from symbiotic incorporation of α-proteobacteria into ancient archaea species. During evolution, mitochondria lost most of the prokaryotic bacterial genes and only conserved a small fraction including those encoding 13 proteins of the respiratory chain. In this process, many functions were transferred to the host cells, but mitochondria gained a central role in the regulation of cell proliferation and apoptosis, and in the modulation of metabolism; accordingly, defective organelles contribute to cell transformation and cancer, diabetes, and neurodegenerative diseases. Most cell and transcriptional effects of mitochondria depend on the modulation of respiratory rate and on the production of...
3.
Does Hyperoxia Selection Cause Adaptive Alterations of Mitochondrial Electron Transport Chain Activity Leading to a Reduction of Superoxide Production? - Zhao, Huiwen W.; Ali, Sameh S.; Haddad, Gabriel G.
Prolonged hyperoxia exposure generates excessive reactive oxygen species (ROS) and potentially leads to oxidative injury in every organ. We have previously generated Drosophila melanogaster flies that tolerate extreme oxidative stress (90%–95% O2), a lethal condition to naive flies, through a long-term laboratory selection. We found that hyperoxia-selected (SO2A) flies had a significantly longer lifespan in hyperoxia and paraquat-induced oxidative stress. Prolonged hyperoxia exposure induced a significant ROS accumulation and an increased expression of oxidative stress markers, including lipid peroxidation and protein carbonyl contents in control flies, but not in SO2A flies. Enzymatic assays revealed that antioxidant enzyme activity in SO2A...
4.
Dietary (Poly)phenolics in Human Health: Structures, Bioavailability, and Evidence of Protective Effects Against Chronic Diseases - Del Rio, Daniele; Rodriguez-Mateos, Ana; Spencer, Jeremy P.E.; Tognolini, Massimiliano; Borges, Gina; Crozier, Alan
Human intervention trials have provided evidence for protective effects of various (poly)phenol-rich foods against chronic disease, including cardiovascular disease, neurodegeneration, and cancer. While there are considerable data suggesting benefits of (poly)phenol intake, conclusions regarding their preventive potential remain unresolved due to several limitations in existing studies. Bioactivity investigations using cell lines have made an extensive use of both (poly)phenolic aglycones and sugar conjugates, these being the typical forms that exist in planta, at concentrations in the low-μM-to-mM range. However, after ingestion, dietary (poly)phenolics appear in the circulatory system not as the parent compounds, but as phase II metabolites, and their...
5.
Toxin Models of Mitochondrial Dysfunction in Parkinson's Disease - Martinez, Terina N.; Greenamyre, J. Timothy
Significance: Parkinson's disease (PD) is a neurodegenerative disorder characterized, in part, by the progressive and selective loss of dopaminergic neuron cell bodies within the substantia nigra pars compacta (SNpc) and the associated deficiency of the neurotransmitter dopamine (DA) in the striatum, which gives rise to the typical motor symptoms of PD. The mechanisms that contribute to the induction and progressive cell death of dopaminergic neurons in PD are multi-faceted and remain incompletely understood. Data from epidemiological studies in humans and molecular studies in genetic, as well as toxin-induced animal models of parkinsonism, indicate that mitochondrial dysfunction occurs early in the...
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Mitochondrial Quality Control and Dynamics in Parkinson's Disease - McCoy, Melissa K.; Cookson, Mark R.
Significance: Studies of sporadic cases, toxin models, and genetic causes of Parkinson's disease suggest that mitochondrial dysfunction may be an early feature of pathogenesis. Recent Advances: Compelling evidence of a causal relationship between mitochondrial function and disease was found with the identification of several genes for recessive parkinsonism, PINK1, DJ-1, and parkin. There is evidence that each of these regulates responses to cellular stresses, including oxidative stress and depolarization of the mitochondrial membrane. Specifically, PINK1 and parkin modulate mitochondrial dynamics by promoting autophagic removal of depolarized mitochondria. Mutations in all genes linked to Parkinson's disease lead to enhanced sensitivity to...
7.
Mitochondrial Permeability Transition Pore Component Cyclophilin D Distinguishes Nigrostriatal Dopaminergic Death Paradigms in the MPTP Mouse Model of Parkinson's Disease - Thomas, Bobby; Banerjee, Rebecca; Starkova, Natalia N.; Zhang, Steven F.; Calingasan, Noel Y.; Yang, Lichuan; Wille, Elizabeth; Lorenzo, Beverly J.; Ho, Daniel J.; Beal, M. Flint; Starkov, Anatoly
Aims: Mitochondrial damage due to Ca2+ overload-induced opening of permeability transition pores (PTP) is believed to play a role in selective degeneration of nigrostriatal dopaminergic neurons in Parkinson's disease (PD). Genetic ablation of mitochondrial matrix protein cyclophilin D (CYPD) has been shown to increase Ca2+ threshold of PTP in vitro and to prevent cell death in several in vivo disease models. We investigated the role of CYPD in a mouse model of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced PD. Results: We demonstrate that in vitro, brain mitochondria isolated from CYPD knockout mice were less sensitive to MPP+ (1-methyl-4-phenyl-pyridinium ion)-induced membrane depolarization, and free radical...
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Mitochondrial Dysfunction in Genetic Animal Models of Parkinson's Disease - Trancikova, Alzbeta; Tsika, Elpida; Moore, Darren J.
Mitochondria are highly dynamic, multifunctional organelles. Aside from their major role in energy metabolism, they are also crucial for many cellular processes including neurotransmission, synaptic maintenance, calcium homeostasis, cell death, and neuronal survival. Significance: Increasing evidence supports a role for abnormal mitochondrial function in the molecular pathophysiology of Parkinson's disease (PD). For three decades we have known that mitochondrial toxins are capable of producing clinical parkinsonism in humans. PD is the most common neurodegenerative movement disorder that is characterized by the progressive loss of substantia nigra dopaminergic neurons leading to a deficiency of striatal dopamine. Although the neuropathology underlying the...
9.
Bacterial Adaptation of Respiration from Oxic to Microoxic and Anoxic Conditions: Redox Control - Bueno, Emilio; Mesa, Socorro; Bedmar, Eulogio J.; Richardson, David J.; Delgado, Maria J.
Under a shortage of oxygen, bacterial growth can be faced mainly by two ATP-generating mechanisms: (i) by synthesis of specific high-affinity terminal oxidases that allow bacteria to use traces of oxygen or (ii) by utilizing other substrates as final electron acceptors such as nitrate, which can be reduced to dinitrogen gas through denitrification or to ammonium. This bacterial respiratory shift from oxic to microoxic and anoxic conditions requires a regulatory strategy which ensures that cells can sense and respond to changes in oxygen tension and to the availability of other electron acceptors. Bacteria can sense oxygen by direct interaction of...
10.
Endoplasmic Reticulum-Dependent Redox Reactions Control Endoplasmic Reticulum-Associated Degradation and Pathogen Entry - Walczak, Christopher P.; Bernardi, Kaleena M.; Tsai, Billy
Significance Protein misfolding within the endoplasmic reticulum (ER) is managed by an ER quality control system that retro-translocates aberrant proteins into the cytosol for proteasomal destruction. This process, known as ER-associated degradation, utilizes the action of ER redox enzymes to accommodate the disulfide-bonded nature of misfolded proteins. Strikingly, various pathogenic viruses and toxins co-opt these redox components to reach the cytosol during entry. These redox factors thus regulate critical cellular homeostasis and host–pathogen interactions. Recent Advances: Recent studies identify specific members of the protein disulfide isomerase (PDI) family, which use their chaperone and catalytic activities, in engaging both misfolded ER...
11.
Mycobacterium tuberculosis WhiB3: A Novel Iron–Sulfur Cluster Protein That Regulates Redox Homeostasis and Virulence - Saini, Vikram; Farhana, Aisha; Steyn, Adrie J.C.
Significance:
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), can persist in a latent state for decades without causing overt disease. Since latent Mtb is refractory to current antimycobacterial drugs, the discovery and characterization of the biological mechanisms controlling the entry, maintenance, and emergence from latent infection is critical to the development of novel clinical therapies. Recent Advances: Recently, Mtb WhiB3, a member of the family of intracellular iron–sulfur (Fe-S) cluster proteins has emerged as a redox sensor and effector molecule controlling several aspects of Mtb virulence. WhiB3 was shown to contain a 4Fe–4S cluster that specifically reacts with important...
12.
Conformational Changes in the Novel Redox Sensor Protein HbpS Studied by Site-Directed Spin Labeling and Its Turnover in Dependence on the Catalase-Peroxidase CpeB - Klare, Johann P.; Ortiz de Orué Lucana, Darío
Aims: To establish conditions to study the oligomeric assembly of heme-binding protein (HbpS) in solution by applying the tools of site-directed spin labeling combined with pulse electron paramagnetic resonance (SDSL EPR) spectroscopy, as well as to analyze redox stress-based conformational changes in HbpS subunits within the oligomer in solution. In vivo elucidation of molecular mechanisms that control the downregulation of the novel redox-system HbpS-SenS-SenR. Results: Using a set of specifically generated HbpS mutants, and SDSL EPR spectroscopy, we show the octomeric assembly of HbpS in solution, and demonstrate that iron-mediated stress induces conformational changes in HbpS subunits within the octamer....
13.
The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities - Huang, Zhi; Rose, Aaron H.; Hoffmann, Peter R.
Dietary selenium (]Se), mainly through its incorporation into selenoproteins, plays an important role in inflammation and immunity. Adequate levels of Se are important for initiating immunity, but they are also involved in regulating excessive immune responses and chronic inflammation. Evidence has emerged regarding roles for individual selenoproteins in regulating inflammation and immunity, and this has provided important insight into mechanisms by which Se influences these processes. Se deficiency has long been recognized to negatively impact immune cells during activation, differentiation, and proliferation. This is related to increased oxidative stress, but additional functions such as protein folding and calcium flux may...
14.
Novel Redox-Sensing Modules: Accessory Protein- and Nucleic Acid-Mediated Signaling - Siedenburg, Gabriele; Groves, Matthew R.; Ortiz de Orué Lucana, Darío
Significance: Organisms have evolved both enzymatic and nonenzymatic pathways to prevent oxidative damage to essential macromolecules, including proteins and nucleic acids. Pathways modulated by different protein-based sensory and regulatory modules ensure a rapid and appropriate response. Recent Advances: In contrast to classical two-component systems that possess internal sensory and regulatory modules, an accessory protein-dependent redox-signaling system has been recently characterized in bacteria. This system senses extracellular iron-mediated oxidative stress signals via an extracellularly located protein (HbpS). In vivo and in vitro studies allowed the elucidation of molecular mechanisms governing this system. Moreover, recent studies show that nucleic acids may also...
15.
Redox Sensing: Novel Avenues and Paradigms - Ortiz de Orué Lucana, Darío
The response to changes in the redox state of the cell environment is closely coupled with the ability of living organisms to sense changing conditions. Protein-based redox sensors utilize cofactors, that is, iron–sulfur clusters, flavins, or hemes, for environmental sensing. Under oxidizing conditions a cofactor-mediated post-translational modification (i.e., thiol-oxidation, carbonylation, or dityrosine formation) accompanied by a structural change in the protein occurs that results in an appropriate reaction, mostly in terms of expression of genes involved in antioxidative stress responses. In addition to these well-studied cofactors, researchers have recently discovered and described redox-active metabolites that play a role in redox...
16.
Redox-Based Regulation of Apoptosis: S-Glutathionylation As a Regulatory Mechanism to Control Cell Death - Anathy, Vikas; Roberson, Elle C.; Guala, Amy S.; Godburn, Karolyn E.; Budd, Ralph C.; Janssen-Heininger, Yvonne M.W.
Significance: Redox-based signaling governs a number of important pathways in tissue homeostasis. Consequently, deregulation of redox-controlled processes has been linked to a number of human diseases. Among the biological processes regulated by redox signaling, apoptosis or programmed cell death is a highly conserved process important for tissue homeostasis. Apoptosis can be triggered by a wide variety of stimuli, including death receptor ligands, environmental agents, and cytotoxic drugs. Apoptosis has also been implicated in the etiology of many human diseases. Recent Advances: Recent discoveries demonstrate that redox-based changes are required for efficient activation of apoptosis. Among these redox changes, alterations in...
17.
Protein Glutathionylation in the Regulation of Peroxiredoxins: A Family of Thiol-Specific Peroxidases That Function As Antioxidants, Molecular Chaperones, and Signal Modulators - Chae, Ho Zoon; Oubrahim, Hammou; Park, Ji Won; Rhee, Sue Goo; Chock, P. Boon
Significance: Reversible protein glutathionylation plays an important role in cellular regulation, signaling transduction, and antioxidant defense. This redox-sensitive mechanism is involved in regulating the functions of peroxiredoxins (Prxs), a family of ubiquitously expressed thiol-specific peroxidase enzymes. Glutathionylation of certain Prxs at their active-site cysteines not only provides reducing equivalents to support their peroxidase activity but also protects Prxs from irreversible hyperoxidation. Typical 2-Cys Prx also functions as a molecular chaperone when it exists as a decamer and/or higher molecular weight complexes. The hyperoxidized sulfinic derivative of 2-Cys Prx is reactivated by sulfiredoxin (Srx). In this review, the roles of glutathionylation...
18.
The Human Paraoxonase Gene Cluster As a Target in the Treatment of Atherosclerosis - She, Zhi-Gang; Chen, Hou-Zao; Yan, Yunfei; Li, Hongliang; Liu, De-Pei
The paraoxonase (PON) gene cluster contains three adjacent gene members, PON1, PON2, and PON3. Originating from the same fungus lactonase precursor, all of the three PON genes share high sequence identity and a similar β propeller protein structure. PON1 and PON3 are primarily expressed in the liver and secreted into the serum upon expression, whereas PON2 is ubiquitously expressed and remains inside the cell. Each PON member has high catalytic activity toward corresponding artificial organophosphate, and all exhibit activities to lactones. Therefore, all three members of the family are regarded as lactonases. Under physiological conditions, they act to degrade metabolites...
19.
Thioredoxin Interacting Protein: Redox Dependent and Independent Regulatory Mechanisms - Spindel, Oded N.; World, Cameron; Berk, Bradford C.
Significance: The thioredoxin-interacting protein (TXNIP, also termed VDUP1 for vitamin D upregulated protein or TBP2 for thioredoxin-binding protein) was originally discovered by virtue of its strong regulation by vitamin D. Recently, TXNIP has been found to regulate the cellular reduction-oxidation (redox) state by binding to and inhibiting thioredoxin (TRX) in a redox-dependent fashion. Recent Advances: Studies of the Hcb-19 mouse, TXNIP nonsense mutated mouse, demonstrate redox-mediated roles in lipid and glucose metabolism, cardiac function, inflammation, and carcinogenesis. Exciting recent data indicate important roles for TXNIP in redox independent signaling. Specifically, sequence analysis revealed that TXNIP is a member of the...
20.
Regulation of Cell Physiology and Pathology by Protein S-Glutathionylation: Lessons Learned from the Cardiovascular System - Pimentel, David; Haeussler, Dagmar Johanna; Matsui, Reiko; Burgoyne, Joseph Robert; Cohen, Richard Alan; Bachschmid, Markus Michael
Significance: Reactive oxygen and nitrogen species contributing to homeostatic regulation and the pathogenesis of various cardiovascular diseases, including atherosclerosis, hypertension, endothelial dysfunction, and cardiac hypertrophy, is well established. The ability of oxidant species to mediate such effects is in part dependent on their ability to induce specific modifications on particular amino acids, which alter protein function leading to changes in cell signaling and function. The thiol containing amino acids, methionine and cysteine, are the only oxidized amino acids that undergo reduction by cellular enzymes and are, therefore, prime candidates in regulating physiological signaling. Various reports illustrate the significance of reversible...
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