Medicine and Health Sciences Commons^™

Lifestyle And Biological Risk Factors For Liver Fibrosis In The Miami Adult Studies On Hiv (Mash) Cohort: An Hiv Infected And Hiv/Hcv Co-Infected Population, Tiffanie S. Stewart

FIU Electronic Theses and Dissertations

Liver disease is now a leading cause of non-AIDS related morbidity and mortality in people living with HIV (PLWH). The present study investigated the interplay between adverse lifestyle factors that are prevalent in PLWH, biological mediators of liver pathogenesis, and a non-invasive measure of liver fibrosis (FIB-4 index) in HIV mono- and HIV/HCV co-infected individuals.

The results of this investigation in the Miami Adult Studies of HIV (MASH) cohort show that the odds of liver fibrosis progression significantly increased over two years for HIV mono-infected participants who drank alcohol hazardously (OR 3.038, P=0.048), and had BMI ≥ 28kg/m^{2 …}

Comparison Of Effects Of Different Antioxidants Supplemented To Long-Term Extender On Boar Semen Quality Following Storage At 17ºc, Thevin Vongpralub, Pachara Thananurak, Chamaiporn Sittikasamkit, Phirawit Chuawongboon, Monchai Duangjinda, Wuttigrai Boonkum, Vibuntita Chankitisakul

The Thai Journal of Veterinary Medicine

The use of antioxidants as semen additives in the extender has been proposed to improve sperm function during cool storage. The objective of this study was to compare the effects of different antioxidant supplementation in extender on boar semen quality during storage for 10 days at 17ºC. Semen samples (n=18) were divided into 10 aliquots and diluted with Reading extender supplemented with three different concentrations of water-soluble glutathione, L-carnitine, and vitamin E analogue Trolox (0.1, 1 and 5mM). All samples were stored in a refrigerator at 17ºC for 10 days. Sperm motility was assessed at Days 1, 4, 7 and …

Low-Dose Aronia Melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity., Adam J. Case, D Agraz, Iman M. Ahmad, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Herbicides containing paraquat may contribute to the pathogenesis of neurodegenerative disorders such as Parkinson's disease. Paraquat induces reactive oxygen species-mediated apoptosis in neurons, which is a primary mechanism behind its toxicity. We sought to test the effectiveness of a commercially available polyphenol-rich Aronia melanocarpa (aronia berry) concentrate in the amelioration of paraquat-induced neurotoxicity. Considering the abundance of antioxidants in aronia berries, we hypothesized that aronia berry concentrate attenuates the paraquat-induced increase in reactive oxygen species and protects against paraquat-mediated neuronal cell death. Using a neuronal cell culture model, we observed that low doses of aronia berry concentrate protected against paraquat-mediated …

Pathophysiologic Mechanisms Of Immune-Mediated Drug Hypersensitivity Reactions To Sulfonamides, Elham A. Sultan

Electronic Thesis and Dissertation Repository

As sulfonamide hypersensitivity reactions are serious clinical problem, it is necessary to determine which patients tolerate therapy and which patients are at risk. Although the exact pathogenesis of these reactions remains unclear, the imbalance in the production and detoxification of reactive sulfamethoxazole (SMX) metabolites appears to be important in the propagation of these reactions. It is known that these reactive metabolites can cause lymphocytes toxicity and produce reactive oxygen species (ROS) which can damage proteins, lipids, and DNA. The hypothesis of this research is that there are differences in cytotoxicity and expression of oxidative stress to reactive SMX metabolites in …

Analysis Of Genetic Diversity Using Simple Sequence Repeat (Ssr) Markers And Growth Regulator Response In Biofield Treated Cotton (Gossypium Hirsutum L.), Mahendra Kumar Trivedi, Alice Branton, Dahryn Trivedi, Gopal Nayak, Mayank Gangwar, Snehasis Jana

Mahendra Kumar Trivedi

Cotton is the most important crop for the production of fiber that plays a key role in economic and social affairs. The aim of the study was to evaluate the impact of biofield energy treatment on cotton seeds regarding its growth, germination of seedling, glutathione (GSH) concentration, indole acetic acid (IAA) content and DNA fingerprinting using simple sequence repeat (SSR) markers for polymorphism analysis. The seeds of cotton cv. Stoneville-2 (Gossypium hirsutum L.) was obtained from DNA Land Marks Inc., Canada and divided into two groups. One group was remained as untreated, while the other was subjected to Mr. Trivedi …

Evaluation Of Plant Growth Regulator, Immunity And Dna Fingerprinting Of Biofield Energy Treated Mustard Seeds (Brassica Juncea), Mahendra Kumar Trivedi, Alice Branton, Dahryn Trivedi, Gopal Nayak, Sambhu Charan Mondal, Snehasis Jana

Mahendra Kumar Trivedi

The Effect Of Red Maple Leaf Toxicosis On Reduced Glutathione Levels In Equine Erythrocytes In Vitro, Madeline A. Rohl

Undergraduate Honors Thesis Projects

Red maple leaf toxicosis is an equine blood disorder resulting from the consumption of wilted red maple (Acer rubrum L.) leaves by horses. Compounds within the leaves of red maple have oxidative effects on equine erythrocytes and can cause hemolysis of erythrocytes, the conversion of hemoglobin to methemoglobin, and the production of Heinz bodies. Reduced glutathione is important in the protection of equine erythrocytes from these oxidative events; however, in the presence of red maple toxin, glutathione is rapidly oxidized and is unavailable. The objective of this study is to determine whether the presence of vitamin C alters levels …

Glutamate And The Biology Of Malignant Glioma, Stephanie Marie Robert

All ETDs from UAB

Malignant gliomas are the most prevalent primary brain tumor. They are highly aggressive and lack effective treatment options. Standard therapy includes a combination of radiation, chemotherapy, and tumor resection; however, even with aggressive treatment, median patient survival remains a dismal 12 – 14 months after diagnosis. Research has focused on understanding the unique biological mechanisms involved in glioma growth and survival in an effort to design novel therapies to treat this devastating disease. In the unique environment of the brain, gliomas have developed the ability to grow and survive at the cost of the normal surrounding brain tissue. Glutamate, the …

Loss Of Multidrug Resistance-Associated Protein 1 (Mrp1/Abcc1) Potentiates Doxorubicin-Induced Cardiotoxicity In Mice, Wei Zhang

Theses and Dissertations--Toxicology and Cancer Biology

Doxorubicin (DOX) is a broad-spectrum and effective chemotherapeutic agent, but its use in oncologic practice is limited by dose-dependent cumulative cardiotoxicity. DOX-induced cardiotoxicity is in large part due to its ability to cause oxidative stress. Multidrug resistance associated protein 1 (MRP1/ABCC1) is a member of the ATP-binding cassette (ABC) transporter superfamily. By effluxing a wide variety of endogenous and exogenous substrates, Mrp1 plays important physiological roles in multiple tissues and also protects normal tissues against toxicants. However, the role of MRP1 in heart is largely unknown.

The role of Mrp1 in DOX-induced cardiotoxicity was investigated in Mrp1 null (Mrp1-/-) and …

Salivary Glucose And Antioxidant Defense Markers In Type Ii Diabetes Mellitus, Sayeeda Mussavira, Mala Dharmalingam, Bindhu Omana Sukumaran

Turkish Journal of Medical Sciences

To evaluate salivary antioxidant defense markers, their correlation with salivary glucose, and glycemic status in type II diabetes mellitus (DM). Materials and methods: The study included 53 diabetic patients and 40 healthy subjects. Salivary glucose, blood glucose, and uric acid (UA) were determined by specific enzymatic methods. Total antioxidant activity (AOA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and total protein were determined spectrophotometrically. Results: Salivary UA (3.12 vs. 1.89 mg/dL), GSH (47 vs. 11.92 µg/mL), and total protein (375.12 vs. 202.23 mg/dL) were significantly higher (P < 0.001; r = 0.455, 0.735, 0.498 respectively) and AOA (653.1 vs. 897.3 µmol/L) was significantly lower in the DM group (P < 0.001, r = -0.431) compared to healthy controls. Among the antioxidant enzymes, CAT was significantly lower (1214 vs. 9468.9 kat) in the DM group (P < 0.001, r = -0.886). Spearman correlation analyses within the diabetic group showed a strong positive association between salivary glucose and blood glucose (P < 0.001, r = 0.9), salivary glucose and GSH, and salivary glucose and UA. Salivary glucose showed a negative correlation with AOA and CAT (P = 0.008, r = -0.447) in the diabetic group. Conclusion: Findings of this study, showing a strong correlation between salivary glucose and blood glucose as well as changes in antioxidant components in the DM group, suggest that saliva can be used for the diagnosis and management of DM.

Glutathione: A Possible Link To Autophagy In Systemic Lupus Erythematosus, Dilip Shah, Swapan K. Nath

Center for Translational Medicine Faculty Papers

No abstract provided.

Profiling Thiol Metabolites And Quantification Of Cellular Glutathione Using Ft-Icr-Ms Spectrometry, Sadakatali S. Gori, Pawel Lorkiewicz, Daniel S. Ehringer, Alex C. Belshoff, Richard M. Higashi, Teresa W-M Fan, Michael H. Nantz

Toxicology and Cancer Biology Faculty Publications

We describe preparation and use of the quaternary ammonium-based α-iodoacetamide QDE and its isotopologue *QDE as reagents for chemoselective derivatization of cellular thiols. Direct addition of the reagents to live cells followed by adduct extraction into n-butanol and analysis by FT-ICR-MS provided a registry of matched isotope peaks from which molecular formulae of thiol metabolites were derived. Acidification to pH 4 during cell lysis and adduct formation further improves the chemoselectivity for thiol derivatization. Examination of A549 human lung adenocarcinoma cells using this approach revealed cysteine, cysteinylglycine, glutathione, and homocysteine as principal thiol metabolites as well as the sulfinic acid …

Aging Aggravates Nitrate-Mediated Ros/Rns Changes., Qian Fan, Lifen Chen, Shujuan Cheng, Fang Li, Wayne Bond Lau, Le Feng Wang, Jing Hua Liu

Department of Emergency Medicine Faculty Papers

Nitrates are the most frequently prescribed and utilized drugs worldwide. The elderly are a major population receiving nitrate therapy. Both nitrates and aging can increase in vivo reactive oxygen species (ROS) and reactive nitrogen species (RNS). To date, the effects of aging upon nitrate-induced ROS/RNS alteration are unknown. The present study tested the effects of aging upon nitrate-induced ROS/RNS alteration in vivo. 32 adults and 43 elderly unstable angina (UA) patients were subjected to 48 hours of isosorbide dinitrate intravenous injection (50  μg/minutes) in this clinical study. Blood samples were obtained at baseline and conclusion. Outcome measures of oxidative stress …

Plasma Selenium Biomarkers In Low Income Black And White Americans From The Southeastern United States, Margaret K. Hargreaves, Jianguo Liu, Maciej S. Buchowski, Kushal A. Patel, Celia O. Larson, David G. Schlundt, Donna M. Kenerson, Kristina E. Hill, Raymond F. Burk, William J. Blot

Public Health, Health Administration, and Health Sciences Faculty Research

Biomarkers of selenium are necessary for assessing selenium status in humans, since soil variation hinders estimation of selenium intake from foods. In this study, we measured the concentration of plasma selenium, selenoprotein P (SEPP1), and glutathione peroxidase (GPX3) activity and their interindividual differences in 383 low-income blacks and whites selected from a stratified random sample of adults aged 40–79 years, who were participating in a long-term cohort study in the southeastern United States (US). We assessed the utility of these biomarkers to determine differences in selenium status and their association with demographic, socio-economic, dietary, and other indicators. Dietary selenium intake …

Glutaredoxin-2 Is Required To Control Oxidative Phosphorylation In Cardiac Muscle By Mediating Deglutathionylation Reactions, Mary-Ellen Harper, Ryan J. Mailloux, Jian Ying Xuan, Skye Mcbride, Wael Maharsy, Stephanie Thorn, Chet E. Holterman, Christopher R.J. Kennedy, Peter Rippstein, Robert Dekemp, Jean Da Silva, Mona Nemer, Marjorie Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin-2 (Grx2) modulates the activity of several mitochondrial proteins in cardiac tissue by catalyzing deglutathionylation reactions. However, it remains uncertain whether Grx2 is required to control mitochondrial ATP output in heart. Here, we report that Grx2 plays a vital role modulating mitochondrial energetics and heart physiology by mediating the deglutathionylation of mitochondrial proteins. Deletion of Grx2 (Grx2−/−) decreased ATP production by complex I-linked substrates to half that in wild type (WT) mitochondria. Decreased respiration was associated with increased complex I glutathionylation diminishing its activity. Tissue glucose uptake was concomitantly increased. Mitochondrial ATP output and complex I activity could be recovered …

Neuroprotective Effects Of Gamma-Glutamylcysteine Ethyl Ester On An In Vivo Moderate Traumatic Brain Injury-Mediated Model And In Vitro In Cortical Astrocytes And Neurons, Jooyoung Cho

Online Theses and Dissertations

Neurodegeneration is the loss of neuronal structures or functions, while neuroprotection is the delay or prevention of neurodegeneration. In traumatic brain injury (TBI), neurodegeneration can occur as the result of oxidative stress, the imbalance of oxidants and antioxidants levels; therefore, antioxidant approaches can be effective therapeutic methods for neuroprotection by attenuating oxidative stress. Glutathione (GSH), a naturally occurring antioxidant, plays an important role in the maintenance of intracellular redox homeostasis by scavenging reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this thesis, we attempted to evaluate the abilities of a GSH precursor, gamma-glutamylcysteine ethyl ester (GCEE), to prevent …

Human Protein Aging: Modification And Crosslinking Through Dehydroalanine And Dehydrobutyrine Intermediates, Zhen Wang, Brian Lyons, Roger J. W Truscott, Kevin L. Schey

Illawarra Health and Medical Research Institute

Nonenzymatic post-translational modification (PTM) of proteins is a fundamental molecular process of aging. The combination of various modifications and their accumulation with age not only affects function, but leads to crosslinking and protein aggregation. In this study, aged human lens proteins were examined using HPLC–tandem mass spectrometry and a blind PTM search strategy. Multiple thioether modifications of Ser and Thr residues by glutathione (GSH) and its metabolites were unambiguously identified. Thirty-four of 36 sites identified on 15 proteins were found on known phosphorylation sites, supporting a mechanism involving dehydroalanine (DHA) and dehydrobutyrine (DHB) formation through β-elimination of phosphoric acid from …

Mrp1: A Target For Hematopoietic Stem Cell Diseases, Cassandra Reiling

Theses and Dissertations--Toxicology and Cancer Biology

Multidrug resistance-associated protein 1 (MRP1) is a member of the adenosine 5’-triphosphate (ATP)-binding cassette (ABC) transporters. MRP1 actively effluxes a variety of endogenous and exogenous substrates from cells, ultimately, working to remove these compounds from the body. MRP1 was initially discovered based on its ability to confer resistance against a variety of chemotherapeutics when overexpressed in cancer cells lines. MRP1 function is important for a number of physiological processes, including regulating cellular and extracellular levels of the anti-inflammatory leukotriene C4 (LTC4) and the antioxidant glutathione (GSH). Our studies have focused on the role of MRP1 in regulating hematopoietic stem cell …

Protective Roles Of Cimin Grape Tissues On Oxidative Stress Markers In The Cellular System Model, Hüseyi̇n Avni̇ Uydu, Ari̇fe Pinar Eki̇nci̇, Mehtap Atak, Adem Demi̇r

Turkish Journal of Medical Sciences

To analyze the phenolic composition of the Cimin grape, which is 1 of 2 grape varieties with a protected geographical indication in Turkey and is used locally to treat the symptoms of some disorders such as impotence and cardiovascular diseases, and to investigate its antioxidant potency against oxidant mediators in the models of intra- and extracellular surroundings. Materials and methods: Cimin grape samples were classified into 5 groups according to the grape's tissues and the extraction solvents used. Free radical scavenging (DPPH) and antilipid peroxidation product [thiobarbituric acid reactive substance (TBARS) and conjugated diene (CD)] levels of the grape tissues …

Glutathione Redox Dynamics And Expression Of Glutathione-Related Genes In The Developing Embryo, Alicia R. Timme-Laragy, Jared V. Goldstone, Barry R. Imhoff, John J. Stegemana, Mark E. Hahn, Jason M. Hansen

Alicia R. Timme-Laragy

Embryonic development involves dramatic changes in cell proliferation and differentiation that must be highly coordinated and tightly regulated. Cellular redox balance is critical for cell fate decisions, but it is susceptible to disruption by endogenous and exogenous sources of oxidative stress. The most abundant endogenous non-protein antioxidant defense molecule is the tri-peptide glutathione (γ-glutamyl-cysteinylglycine, GSH), but the ontogeny of GSH concentration and redox state during early life stages is poorly understood. Here, we describe the GSH redox dynamics during embryonic and early larval development (0–5 days post-fertilization) in the zebrafish (Danio rerio), a model vertebrate embryo. We measured reduced and …

Oxidative Stress For An Acute Bout Of Bikram Yoga In Healthy, Trained Adults, Kimberly Anne Trocio

UNLV Theses, Dissertations, Professional Papers, and Capstones

BACKGROUND:Generation of free radicals resulting in oxidative damage has been linked to cellular damage, aging, and human disease. Many studies have reported that physical exercise can contribute to oxidative stress. Further, exercise in a hyperthermic environment can promote additional oxidative stress. It is important to consider that practices in yoga may be beneficial in reducing oxidative stress according to some studies. The compound effects of exercise and hyperthermic exposure are experienced in the practice of Bikram yoga, the original "hot" yoga. Because Bikram yoga and other hot exercise classes are an increasingly growing fitness trend, it is necessary to investigate …

Pulmonary Dwcnt Exposure Causes Sustained Local And Low-Level Systemic Inflammatory Changes In Mice, Furong Tian, Junja C. Habel-Ungewitter, Yin Renfu, Tobias Stoger

Articles

Carbon nanotubes (CNTs) represent promising vectors to facilitate cellular drug delivery and to overcome biological barriers, but some types may also elicit persistent pulmonary inflammation based on their fibre characteristics. Here, we show the pulmonary response to aqueous suspensions of block copolymer dispersed, double-walled carbon nanotubes (DWCNT, length 1–10 lm) in mice by bronchoalveolar lavage (BAL) analysis, and BAL and blood cytokine and lung antioxidant profiling. The intratracheally instilled dose of 50 lg DWCNT caused significant pulmonary inflammation that was not resolved during a 7- day observation period. Light microscopy investigation of the uptake of DWCNT agglomerates revealed no particle …

Structural Insights Into Omega-Class Glutathione Transferases: A Snapshot Of Enzyme Reduction And Identification Of A Non-Catalytic Ligandin Site, Joseph Brock, Philip G. Board, Aaron J. Oakley

Faculty of Science, Medicine and Health - Papers: part A

Glutathione transferases (GSTs) are dimeric enzymes containing one active-site per monomer. The omega-class GSTs (hGSTO1-1 and hGSTO2-2 in humans) are homodimeric and carry out a range of reactions including the glutathione-dependant reduction of a range of compounds and the reduction of S-(phenacyl)glutathiones to acetophenones. Both types of reaction result in the formation of a mixed-disulfide of the enzyme with glutathione through the catalytic cysteine (C32). Recycling of the enzyme utilizes a second glutathione molecule and results in oxidized glutathione (GSSG) release. The crystal structure of an active-site mutant (C32A) of the hGSTO1-1 isozyme in complex with GSSG provides a snapshot …

Effect Of Nrf2 Activators On Release Of Glutathione, Cysteinylglycine And Homocysteine By Human U373 Astroglial Cells, Megan L. Steele, Stacey Fuller, Mili Patel, Cindy Kersaitis, Lezanne Ooi, Gerald Munch

Faculty of Science, Medicine and Health - Papers: part A

Neurons rely on the release and subsequent cleavage of GSH to cysteinylglycine (CysGly) by astrocytes in order to maintain optimal intracellular GSH levels. In neurodegenerative diseases characterised by oxidative stress, neurons need an optimal GSH supply to defend themselves against free radicals released from activated microglia and astroglia. The rate of GSH synthesis is controlled largely by the activity of γ-glutamyl cysteine ligase. Expression of γ-glutamyl cysteine ligase and of the Xc- system, which facilitates cystine uptake, is regulated by the redox-sensitive transcription factor, nuclear factor erythroid-2-related factor 2 (Nrf2). Compounds that can activate the Nrf2-ARE pathway, referred to as …

Comparison Of The Antioxidant System Response To Melatonin Implant In Raccoon Dog (Nyctereutes Procyonoides) And Silver Fox (Vulpes Vulpes), Svetlana Sergina, Irina Baishnikova, Viktor Ilyukha, Marcin Lis, Stanislaw Lapinski, Piotr Niedbala, Boguslaw Barabasz

Turkish Journal of Veterinary & Animal Sciences

The aim of this work was to investigate whether melatonin implant may modify the response of the antioxidant systems of raccoon dog and silver fox. Animals of each species were divided into 2 equal groups: implanted with 12 mg of melatonin in late June and not implanted (control). During the standard fur production process in late November, samples of tissues (liver, kidney, spleen, and heart) were collected and specific activities of superoxide dismutase (SOD) and catalase (CAT), and the contents of reduced glutathione (GSH), retinol, α-tocopherol (TCP), and total tissue protein, were determined in tissue samples. Activity of antioxidant enzymes …

Pyocyanin-Induced Toxicity In A549 Respiratory Cells Is Causally Linked To Oxidative Stress, Lee Gloyne, Gary Grant, Anthony Perkins, Katie Powell, Catherine Mcdermott, Peter Johnson, Gregory Anderson, Milton Kiefel, Shailendra Anoopkumar-Dukie

Catherine M. McDermott

Pyocyanin, a virulence factor produced by Pseudomonas aeruginosa, has many damaging effects on mammalian cells. Several lines of evidence suggest that this damage is primarily mediated by its ability to generate ROS and deplete host antioxidant defence mechanisms. However, a causal role for oxidative stress has not yet been demonstrated conclusively. Parallel measures of ROS production, antioxidant levels and cytotoxicity provide convincing evidence that pyocyanin-induced cytotoxicity in A549 respiratory cells is mediated by acute ROS production and subsequent oxidative stress. Pyocyanin increased ROS levels in A549 cells as measured by the fluorescent H2O2 probes Amplex Red and DCFH-DA. These effects …

Trpm2 In The Central Nervous System: Physiological Role And Critical Regulatory Pathways, Jillian C. Belrose

Electronic Thesis and Dissertation Repository

TRPM2 is a non-selective cation channel which is permeable to calcium. Although expression is highest in the brain, the physiological role for TRPM2 in neurons was unknown. Furthermore, our understanding of the pathways regulating TRPM2 channel function required further investigation. In this thesis, we identified that TRPM2 is required for NMDAR-dependent long-term depression (LTD). No change in NMDAR expression or function was observed following genetic deletion of TRPM2. Instead, the loss of NMDAR-LTD in TRPM2 knockout mice results from diminished GSK-3β activation. We next examined whether age in vitro could facilitate TRPM2 currents. We demonstrate that diminished glutathione with age …

Glutathione-Mediated Neuroprotection Against Methylmercury Neurotoxicity In Cortical Culture Is Dependent On Mrp1, Travis Rush, Xiaoqian Liu, Andrew B. Nowakowski, David H. Petering, Doug Lobner

Biomedical Sciences Faculty Research and Publications

Methylmercury (MeHg) exposure at high concentrations poses significant neurotoxic threat to humans worldwide. The present study investigated the mechanisms of glutathione-mediated attenuation of MeHg neurotoxicity in primary cortical culture. MeHg (5 μM) caused depletion of mono- and disulfide glutathione in neuronal, glial and mixed cultures. Supplementation with exogenous glutathione, specifically glutathione monoethyl ester (GSHME) protected against the MeHg induced neuronal death. MeHg caused increased reactive oxygen species (ROS) formation measured by dichlorodihydrofluorescein (DCF) fluorescence with an early increase at 30 min and a late increase at 6 h. This oxidative stress was prevented by the presence of either GSHME or …

Free Cysteine Modulates The Conformation Of Human C/Ebp Homologous Protein, Vinay K. Singh, Mona M. Rahman, Kim Munro, Vladimir N. Uversky, Steven P. Smith, Zongchao Jia

Molecular Medicine Faculty Publications

The C/EBP Homologous Protein (CHOP) is a nuclear protein that is integral to the unfolded protein response culminating from endoplasmic reticulum stress. Previously, CHOP was shown to comprise extensive disordered regions and to self-associate in solution. In the current study, the intrinsically disordered nature of this protein was characterized further by comprehensive in silico analyses. Using circular dichroism, differential scanning calorimetry and nuclear magnetic resonance, we investigated the global conformation and secondary structure of CHOP and demonstrated, for the first time, that conformational changes in this protein can be induced by the free amino acid l-cysteine. Addition of l-cysteine caused …

Physiological And Toxicological Roles Of Abc Transporters In Cellular Efflux Of Substrates, Donna J. Coy

Theses and Dissertations--Toxicology and Cancer Biology

ATP-binding cassette (ABC) transporters are transmembrane proteins that transport a wide variety of substrates across intra and extra-cellular membranes. A few examples of endo and xenobiotic substrates are metabolic products, lipids, sterols, and drugs. An important function of ABC transporters involved in export is to prevent intracellular the buildup of toxic products. Several ABC transporters have also been associated with drug resistance upon treatment with chemotherapeutic agents. P-glycoprotein (P-GP) and the multidrug resistant (MRP) transporters of the ABC C family are examples of transporters that confer chemo-resistance.

We have studied two unique roles of ABC transporters in the liver and …