Depletion of protein thiols and the accumulation of oxidized thioredoxin in Parkinsonism disclosed by a red-emitting and environment-sensitive probe

2019 ◽  
Vol 7 (16) ◽  
pp. 2696-2702 ◽  
Author(s):  
Guodong Hu ◽  
Baoxin Zhang ◽  
Pengcheng Zhou ◽  
Yanan Hou ◽  
Huiyi Jia ◽  
...  
Keyword(s):  
Redox Homeostasis ◽  
Vital Role ◽  
Low Molecular Weight ◽  
Selective Detection ◽  
Cellular Redox ◽  
P Protein ◽  
Protein Thiols ◽  
Protein Functions ◽  
Protein Sulfhydryl ◽  
Protein Sulfhydryl Groups

Protein sulfhydryl groups play a vital role in maintaining cellular redox homeostasis and protein functions and have attracted increasing interests for the selective detection of protein thiols over low-molecular-weight thiols (LMWTs).

Mitochondria-Targeted Ratiometric Fluorescent Imaging of Cysteine

The Analyst ◽  
2021 ◽  
Author(s):  
Ya-Nan Wei ◽  
Bo Lin ◽  
Yang Shu ◽  
Jian-Hua Wang
Keyword(s):  
Reactive Oxygen Species ◽  
Redox Homeostasis ◽  
Reactive Oxygen ◽  
Fluorescent Imaging ◽  
Oxygen Species ◽  
Cellular Redox ◽  
Critical Part ◽  
Physiological Processes

As an indispensable biothiol, cysteine (Cys) plays a critical part in cellular redox homeostasis, pathological and physiological processes. One of the main sources of reactive oxygen species (ROS) in human...

scholarly journals Micro RNAs in Regulation of Cellular Redox Homeostasis

2021 ◽  
Vol 22 (11) ◽  
pp. 6022
Author(s):  
Sylwia Ciesielska ◽  
Izabella Slezak-Prochazka ◽  
Patryk Bil ◽  
Joanna Rzeszowska-Wolny
Keyword(s):  
Target Genes ◽  
Redox Homeostasis ◽  
Messenger Rnas ◽  
Cellular Redox ◽  
Cell Responses ◽  
Regulatory Circuits ◽  
Micro Rnas ◽  
Cellular Behaviors ◽  
Homeostasis Regulation ◽  
Thioredoxin Reductases

In living cells Reactive Oxygen Species (ROS) participate in intra- and inter-cellular signaling and all cells contain specific systems that guard redox homeostasis. These systems contain both enzymes which may produce ROS such as NADPH-dependent and other oxidases or nitric oxide synthases, and ROS-neutralizing enzymes such as catalase, peroxiredoxins, thioredoxins, thioredoxin reductases, glutathione reductases, and many others. Most of the genes coding for these enzymes contain sequences targeted by micro RNAs (miRNAs), which are components of RNA-induced silencing complexes and play important roles in inhibiting translation of their targeted messenger RNAs (mRNAs). In this review we describe miRNAs that directly target and can influence enzymes responsible for scavenging of ROS and their possible role in cellular redox homeostasis. Regulation of antioxidant enzymes aims to adjust cells to survive in unstable oxidative environments; however, sometimes seemingly paradoxical phenomena appear where oxidative stress induces an increase in the levels of miRNAs which target genes which are supposed to neutralize ROS and therefore would be expected to decrease antioxidant levels. Here we show examples of such cellular behaviors and discuss the possible roles of miRNAs in redox regulatory circuits and further cell responses to stress.

A Survey for Predicting ATP Binding Residues of Proteins Using Machine Learning Methods

2021 ◽  
Vol 28 ◽  
Author(s):  
Yu-He Yang ◽  
Jia-Shu Wang ◽  
Shi-Shi Yuan ◽  
Meng-Lu Liu ◽  
Wei Su ◽  
...  
Keyword(s):  
Machine Learning ◽  
Protein Function ◽  
Vital Role ◽  
Atp Binding ◽  
Learning Methods ◽  
Machine Learning Methods ◽  
Protein Ligand Interactions ◽  
Protein Functions ◽  
Ligand Interactions ◽  
Binding Residues

: Protein-ligand interactions are necessary for majority protein functions. Adenosine-5’-triphosphate (ATP) is one such ligand that plays vital role as a coenzyme in providing energy for cellular activities, catalyzing biological reaction and signaling. Knowing ATP binding residues of proteins is helpful for annotation of protein function and drug design. However, due to the huge amounts of protein sequences influx into databases in the post-genome era, experimentally identifying ATP binding residues is cost-ineffective and time-consuming. To address this problem, computational methods have been developed to predict ATP binding residues. In this review, we briefly summarized the application of machine learning methods in detecting ATP binding residues of proteins. We expect this review will be helpful for further research.

Interaction of surfactant mixtures with reactive oxygen and nitrogen species

1995 ◽  
Vol 78 (5) ◽  
pp. 1800-1805 ◽  
Author(s):  
J. Cifuentes ◽  
J. Ruiz-Oronoz ◽  
C. Myles ◽  
B. Nieves ◽  
W. A. Carlo ◽  
...  
Keyword(s):  
Lung Surfactant ◽  
Alveolar Epithelium ◽  
Reactive Species ◽  
Surfactant Mixtures ◽  
Surfactant Deficiency ◽  
High Lipid ◽  
Fenton Reagents ◽  
Protein Sulfhydryl ◽  
Nitrogen Reactive Species ◽  
Protein Sulfhydryl Groups

Increased concentrations of partially reduced oxygen and nitrogen reactive species damage the alveolar epithelium and either cause or exacerbate surfactant deficiency. For this reason, there is a quest to identify surfactant replacement mixtures, which in addition to repleting depleted surfactant stores can also reduce the steady-state concentrations of reactive species in the alveolar space. Herein, we evaluated the ability of natural lung surfactant (NLS) and two mixtures (Exosurf and Survanta) used clinically for the correction of surfactant deficiency to scavenge hydroxyl radical-type species (.OH), generated either by the decomposition of peroxynitrite or by Fenton reagents (FeCl3 + H2O2). Exosurf or Survanta decreased .OH only when present at high lipid concentrations (6.5 mM). On the other hand, 40 microM of NLS decreased .OH concentrations from 75 +/- 2 to 53 +/- 2 microM (P < 0.05), most likely because of the interaction of .OH with protein sulfhydryl groups. Similarly, 40 microM of NLS incubated with a bolus of H2O2 (400 microM) decreased the H2O2 concentration in the supernatant by approximately 50%, due to the presence of catalase-type activity. In contrast to NLS, neither Exosurf nor Survanta scavenged H2O2, even when present at millimolar lipid concentrations. We concluded that Exosurf and Survanta contain limited antioxidant activity compared with NLS.

scholarly journals Endogenous formaldehyde scavenges cellular glutathione resulting in cytotoxic redox disruption

2020 ◽  
Author(s):  
Carla Umansky ◽  
Agustín Morellato ◽  
Marco Scheidegger ◽  
Matthias Rieckher ◽  
Manuela R. Martinefski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Redox Homeostasis ◽  
Thiol Group ◽  
Cellular Damage ◽  
Repair Pathway ◽  
Cellular Redox ◽  
Redox Active ◽  
Development And Aging

AbstractFormaldehyde (FA) is a ubiquitous endogenous and environmental metabolite that is thought to exert cytotoxicity through DNA and DNA-protein crosslinking. We show here that FA can cause cellular damage beyond genotoxicity by triggering oxidative stress, which is prevented by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR). Mechanistically, we determine that endogenous FA reacts with the redox-active thiol group of glutathione (GSH) forming S-hydroxymethyl-GSH, which is metabolized by ADH5 yielding reduced GSH thus preventing redox disruption. We identify the ADH5-ortholog gene in Caenorhabditis elegans and show that oxidative stress also underlies FA toxicity in nematodes. Moreover, we show that endogenous GSH can protect cells lacking the Fanconi Anemia DNA repair pathway from FA, which might have broad implications for Fanconi Anemia patients and for healthy BRCA2-mutation carriers. We thus establish a highly conserved mechanism through which endogenous FA disrupts the GSH-regulated cellular redox homeostasis that is critical during development and aging.

scholarly journals Gankyrin has an antioxidative role through the feedback regulation of Nrf2 in hepatocellular carcinoma

2016 ◽  
Vol 213 (5) ◽  
pp. 859-875 ◽  
Author(s):  
Chun Yang ◽  
Ye-xiong Tan ◽  
Guang-zhen Yang ◽  
Jian Zhang ◽  
Yu-fei Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatocellular Carcinoma ◽  
Redox Homeostasis ◽  
Feedback Regulation ◽  
Cellular Redox ◽  
Intracellular Ros ◽  
Oxidative Stress Status ◽  
Kelch Domain ◽  
Cellular Stressors ◽  
Hcc Cells

Oxidative stress status has a key role in hepatocellular carcinoma (HCC) development and progression. Normally, reactive oxygen species (ROS) levels are tightly controlled by an inducible antioxidant program that responds to cellular stressors. How HCC cells respond to excessive oxidative stress remains elusive. Here, we identified a feedback loop between gankyrin, an oncoprotein overexpressed in human HCC, and Nrf2 maintaining the homeostasis in HCC cells. Mechanistically, gankyrin was found to interact with the Kelch domain of Keap1 and effectively competed with Nrf2 for Keap1 binding. Increased expression of gankyrin in HCC cells blocked the binding between Nrf2 and Keap1, inhibiting the degradation of Nrf2 by proteasome. Interestingly, accumulation and translocation of Nrf2 increased the transcription of gankyrin through binding to the ARE elements in the promoter of gankyrin. The positive feedback regulation involving gankyrin and Nrf2 modulates a series of antioxidant enzymes, thereby lowering intracellular ROS and conferring a steadier intracellular environment, which prevents mitochondrial damage and cell death induced by excessive oxidative stress. Our results indicate that gankyrin is a regulator of cellular redox homeostasis and provide a link between oxidative stress and the development of HCC.

scholarly journals S-Adenosylmethionine Deficiency and Brain Accumulation of S-Adenosylhomocysteine in Thioacetamide-Induced Acute Liver Failure

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2135
Author(s):  
Anna Maria Czarnecka ◽  
Wojciech Hilgier ◽  
Magdalena Zielińska
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Redox Homeostasis ◽  
Cerebral Function ◽  
Total Glutathione ◽  
Cellular Redox ◽  
Therapeutic Value ◽  
Transsulfuration Pathway ◽  
Subsequent Hydrolysis ◽  
The Brain

Background: Acute liver failure (ALF) impairs cerebral function and induces hepatic encephalopathy (HE) due to the accumulation of neurotoxic and neuroactive substances in the brain. Cerebral oxidative stress (OS), under control of the glutathione-based defense system, contributes to the HE pathogenesis. Glutathione synthesis is regulated by cysteine synthesized from homocysteine via the transsulfuration pathway present in the brain. The transsulfuration-transmethylation interdependence is controlled by a methyl group donor, S-adenosylmethionine (AdoMet) conversion to S-adenosylhomocysteine (AdoHcy), whose removal by subsequent hydrolysis to homocysteine counteract AdoHcy accumulation-induced OS and excitotoxicity. Methods: Rats received three consecutive intraperitoneal injections of thioacetamide (TAA) at 24 h intervals. We measured AdoMet and AdoHcy concentrations by HPLC-FD, glutathione (GSH/GSSG) ratio (Quantification kit). Results: AdoMet/AdoHcy ratio was reduced in the brain but not in the liver. The total glutathione level and GSH/GSSG ratio, decreased in TAA rats, were restored by AdoMet treatment. Conclusion: Data indicate that disturbance of redox homeostasis caused by AdoHcy in the TAA rat brain may represent a deleterious mechanism of brain damage in HE. The correction of the GSH/GSSG ratio following AdoMet administration indicates its therapeutic value in maintaining cellular redox potential in the cerebral cortex of ALF rats.

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