Chemistry Commons^™

Glutathione And Glutaredoxin—Key Players In Cellular Redox Homeostasis And Signaling, Yuh-Cherng Chai, John J. Mieyal

2023 Faculty Bibliography

This Special Issue of Antioxidants on Glutathione (GSH) and Glutaredoxin (Grx) was designed to collect review articles and original research studies focused on advancing the current understanding of the roles of the GSH/Grx system in cellular homeostasis and disease processes. The tripeptide glutathione (GSH) is the most abundant non-enzymatic antioxidant/nucleophilic molecule in cells. In addition to various metabolic reactions involving GSH and its oxidized counterpart GSSG, oxidative post-translational modification (PTM) of proteins has been a focal point of keen interest in the redox field over the last few decades. In particular, the S-glutathionylation of proteins (protein-SSG formation), i.e., mixed disulfides …

Thiol Antioxidants Protect Human Lens Epithelial (Hle B-3) Cells Against Tert-Butyl Hydroperoxide-Induced Oxidative Damage And Cytotoxicity, Annalise Pfaff, Anna Chernatynskaya, Hannah Vineyard, Nuran Ercal

Chemistry Faculty Research & Creative Works

Oxidative damage to lens epithelial cells plays an important role in the development of age-related cataract, and the health of the lens has important implications for overall ocular health. As a result, there is a need for effective therapeutic agents that prevent oxidative damage to the lens. Thiol antioxidants such as tiopronin or N-(2-mercaptopropionyl)glycine (MPG), N-acetylcysteine amide (NACA), N-acetylcysteine (NAC), and exogenous glutathione (GSH) may be promising candidates for this purpose, but their ability to protect lens epithelial cells is not well understood. The effectiveness of these compounds was compared by exposing human lens epithelial cells (HLE B-3) to the …

Extensive Thiol Profiling For Assessment Of Intracellular Redox Status In Cultured Cells By Hplc-Ms/Ms, Jiandong Wu, Anna Chernatynskaya, Annalise Pfaff, Huari Kou, Nan Cen, Nuran Ercal, Honglan Shi

Computer Science Faculty Research & Creative Works

Oxidative stress may contribute to the pathology of many diseases, and endogenous thiols, especially glutathione (GSH) and its metabolites, play essential roles in the maintenance of normal redox status. Understanding how these metabolites change in response to oxidative insult can provide key insights into potential methods of prevention and treatment. Most existing methodologies focus only on the GSH/GSH disulfide (GSSG) redox couple, but GSH regulation is highly complex and depends on several pathways with multiple redox-active sulfur-containing species. In order to more fully characterize thiol redox status in response to oxidative insult, a high-performance liquid chromatography with tandem mass spectrometry …

Hydrogen Peroxide Triggers An Increase In Cell Surface Expression Of System XC− In Cultured Human Glioma Cells, Leah A. Chase, Mary Verheulen Kleyn, Natasha Schiller, Abby Goltz King, Guillermo Flores, Sasha Balcazar Engelsman, Christina Bowles, Sara Lang Smith, Anne E. Robinson, Jeffrey Rothstein

Faculty Publications

System x_c⁻ exchanges extracellular cystine for intracellular glutamate across the plasma membrane of many cell types. One of the physiological roles of System x_c⁻ is to provide cystine for synthesis of the antioxidant glutathione. Here we report that hydrogen peroxide (H₂O₂) triggers the translocation of System x_c⁻ to the plasma membrane within 10 min of the initial exposure. Specifically, we observed a three-fold increase in ³⁵S-L-cystine uptake following a 10 min exposure to 0.3 mM H₂O₂. This effect was dose-dependent with an EC₅₀ for …

The Protective Effect Of N-Acetylcysteine Amide Against Paraquat-Induced Neurotoxicity, Burhan Ates, Nigar Vardi, Hakan Parlakpinar, Merve Goksin Karaaslan, Ismet Yilmaz, Nuran Ercal

Chemistry Faculty Research & Creative Works

N-acetylcysteine amide (NACA) is a new antioxidant molecule with powerful radical scavenging properties. The aim of this study was to investigate neuroprotective effects of NACA against paraquat (PQ) toxicity in the midbrains of rats by using motor coordination tests and biochemical and histological analysis. Thirty adult Wistar albino rats were divided into three groups: Group 1: control (n = 10), Group 2: PQ (10 mg/kg) (n = 10), and Group 3: PQ (10 mg/kg) + NACA (100 mg/kg) (n = 10). NACA was administrated intraperitoneally 30 min before PQ injection. Performance was measured for a period of 28 days. The …

Biosensor For The Oxidative Stress Biomarker Glutathione Based On Sam Of Cobalt Phthalocyanine On A Thioctic Acid Modified Gold Electrode, Mohammed Nooredeen Abbas, Ayman Ali Saeed, Mounir Ben Ali, Abdelhamid Errachid, Nadia Zine, Abdullatif Baraket, Baljit Singh

Articles

Self-assembled monolayer (SAM) of cobalt teraaminophthalocyanine (CoTAPc) was developed on thioctic acid (TA) dithiol modified gold electrode and electrochemically evaluated as a glutathione (GSH) selective biosensor. The CoTAPc-TA-Au modified electrode was developed by the covalent immobilization of the CoTAPc as the electrochemical mediator onto previously prepared gold electrode modified with TA (TA-Au) via amid bond formation with the carboxylic group of TA, producing well-organized SAM of the mediator. For comparison, another electrode modified with 3-mercaptopropionic acid (MPA) as a monothiol linker instead of TA was similarly prepared. The electrode surface modification was characterized using SEM, AFM, CV, and EIS. The …

Glutathione: A Small Molecule With Big Sense, Cristina E. Raya, Debasish Bandyopadhyay

Chemistry Faculty Publications and Presentations

Glutathione, a peptide found in microbes, plants and animals including human plays a key role in maintaining healthy cells. The peptide exists in both reduced and oxidized forms. Synthesis of GSH occurs in the cytosol of cells, and the extent of glutathione synthesis relies on various factors, such as amino acid availability, protein activity etc. Once synthesized, glutathione exists in both forms: oxidized (GSSG) and reduced (GSH). Oxidized glutathione characterized by its disulfide linkage. On the other hand, presence of a thiol group characterizes the reduced glutathione. This thiol makes the tripeptide an essential component of health; it makes glutathione …

Prevention And Reversal Of Selenite-Induced Cataracts By N-Acetylcysteine Amide In Wistar Rats, Yasaswi Maddirala, Shakila Tobwala, Humeyra Karacal, Nuran Ercal

Chemistry Faculty Research & Creative Works

Background: The present study sought to evaluate the efficacy of N-acetylcysteine amide (NACA) eye drops in reversing the cataract formation induced by sodium selenite in male Wistar rat pups.

Methods: Forty male Wistar rat pups were randomly divided into a control group, an N-acetylcysteine amide-only group, a sodium selenite-induced cataract group, and a NACA-treated sodium selenite-induced cataract group. Sodium selenite was injected intraperitoneally on postpartum day 10, whereas N-acetylcysteine amide was injected intraperitoneally on postpartum days 9, 11, and 13 in the respective groups. Cataracts were evaluated at the end of week 2 (postpartum day 14) when the rat pups …

Chemotherapeutic Drug Design: An Efficient Synthesis Of 4-Substituted Alpha-Methylene-Gamma-Lactones, Mark F. Mechelke, Katy Platt, Connor Pribula

Chemistry Faculty Publications

Sesquiterpene lactones are plant-derived compounds that have been shown to possess significant activity against inflammation and cancer. Comparative studies of sesquiterpene lactone structure and tumor cytotoxicity indicate that the presence of an α-methylene-γ-lactone moiety is necessary for bioactivity. This observation has led to the hypothesis that simple compounds containing this pharmacophore may also exhibit similar anti-cancer properties. To test this theory, an efficient synthesis of 4-substituted α-methylene-γ-lactone has been developed. The model compound in this study, α-methylene-γ-dodecalactone, has been prepared from commercially available 1-decene in six steps. The synthesis features a nucleophilic epoxide ring-opening reaction followed by an intramolecular cyclization …

The Interaction Of Glutathione With Platinum, And The Role Of Ph In Altering Ligand Formation Between Platinum And N-Acetylcysteine, Kyle B. Mann

Mahurin Honors College Capstone Experience/Thesis Projects

Cisplatin is an important anti-cancer drug. Structurally, cisplatin is a coordination complex, which means that it has a central metallic atom: platinum. Side interactions prevent cisplatin from effectively treating cancerous cells by reaction with DNA. Cisplatin has a high rate of forming protein adducts, primarily with sulfur containing amino acids. To better understand how cisplatin interacts with sulfur containing amino acids in the body, a platinum compound with an ethylenediamine ligand attached was reacted with N-acetylcysteine and glutathione. The reactions of cysteine with platinum were performed at three pH values: 7.0, 8.5, and 10. NMR spectroscopy was used to examine …

Thimerosal Exposure And The Role Of Sulfation Chemistry And Thiol Availability In Autism, Janet K. Kern, Boyd E. Haley, David A. Geier, Lisa K. Sykes, Paul G. King, Mark R. Geier

Chemistry Faculty Publications

Autism spectrum disorder (ASD) is a neurological disorder in which a significant number of the children experience a developmental regression characterized by a loss of previously acquired skills and abilities. Typically reported are losses of verbal, nonverbal, and social abilities. Several recent studies suggest that children diagnosed with an ASD have abnormal sulfation chemistry, limited thiol availability, and decreased glutathione (GSH) reserve capacity, resulting in a compromised oxidation/reduction (redox) and detoxification capacity. Research indicates that the availability of thiols, particularly GSH, can influence the effects of thimerosal (TM) and other mercury (Hg) compounds. TM is an organomercurial compound (49.55% Hg …

Lipid Peroxides And Glutathione Status In Human Progenitor Mononuclear (U937) Cells Following Exposure To Low Doses Of Nickel And Copper, William Y. Boadi, Shalandus Harris, Justin B. Anderson, Samuel E. Adunyah

Chemistry Faculty Research

Effects of Cu2+, Ni2+ or Cu2+ + Ni2+ on lipid peroxide and glutathione (GSH) levels in U937 cells were investigated. Cells were treated with 0, 5, 10, and 20 µM of Cu2+ and/or Ni2+ and H2O2 (0.01 mM) and incubated for 24 hours at 37°C. Lipid peroxides were measured by the thiobarbituric acid assay (TBA). GSH intracellular levels were assayed by the GSH assay kit from EMD/Calbiochem (San Diego, California, USA). Cu2+ or Ni2+ significantly (P < 0.01) increased lipid peroxides in a dose-dependent manner, compared to controls. The effect was more pronounced for Cu2+, compared to the Ni2+-treated samples. Cu2+ + Ni2+ increased lipid peroxides in a significant (P < 0.001), dose-dependent manner, compared to Cu2+ or Ni2+ alone (i.e., ratio of 2.5:1-fold for combined versus single treatments, respectively). Cu2+ or Ni2+ significantly decreased GSH levels in U937 cells, with the effect being pronounced for Cu2+. Cu2+ + Ni2+ metal ions significantly (P < 0.001) depleted cells of GSH in a dose-dependent manner. Ethylene diamine tetraacetic acid (EDTA) at 50 or 100 µM moderately reduced the Cu2+- or Ni2+-induced effects on GSH levels. Interestingly, GSH levels generally decreased to half (except for the combined metal dose of 20 µM at 100 µM EDTA) of its level at the highest metal concentration tested for both the single or combined treatments. In conclusion, multiple exposures of cells to metal ions may be lethal to cells, compared to their single treatments.

Effects Of N-Acetylcysteine And 2,3-Dimercaptosuccinic Acid On Lead Induced Oxidative Stress In Rat Lenses, Rachel Neal, Katherine Cooper, Nuran Ercal, Hande Gürer-Orhan

Chemistry Faculty Research & Creative Works

Lead (Pb) is known to disrupt the pro-oxidant/anti-oxidant balance of tissues which leads to biochemical and physiological dysfunction. The present study investigated the previous termeffectsnext term of exposure on the redox status of the lenses of Fisher 344 rats and examined whether antioxidant or chelator administration reversed these changes. Animals were given 5 weeks of 2000 ppm Pb exposure followed by 1 week of either antioxidant, chelator or distilled water administration. Glutathione (GSH) and cysteine (CYS) levels decreased in the Pb-exposed group. N-previous termacetylcysteinenext term or 2,3-dimercaptopsuccinic previous termacidnext term (Succimer) supplementation following Pb intoxication resulted in increases in the …