Loss Of Thiol Repair Systems In Human Cataractous Lenses, Min Wei, Kui-Yi Xing, Yin-Chuan Fan, Teodosio Libondi, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. The purpose of this study was to investigate the thiol repair systems of thioltransferase (TTase) and thioredoxin (Trx) and oxidation-damaged proteins in human cataractous lenses.

METHODS. Cataractous lenses in humans (57–85 years of age) were classified into cortical, nuclear, mixed, mature, and hypermature cataract types by using a lens opacity classification system, and were obtained by extracapsular cataract extraction (ECCE) procedure. Cortical and nuclear cataracts were grouped by decreasing order of visual acuity into optical chart reading (R), counting fingers (CF), hand motion (HM), and light perception (LP). ECCE lens homogenate was analyzed for glutathione (GSH) level and enzyme …

Regulation Of The High-Affinity Choline Transporter Activity And Trafficking In Alzheimer’S Disease-Related Pathological Conditions, Leah K. Cuddy

Electronic Thesis and Dissertation Repository

Cholinergic neurons play a key role in cognitive processes through the action of the neurotransmitter acetylcholine (ACh). Dysfunction of these neurons occurs in several neurodegenerative disorders, including Alzheimer’s disease (AD). The high-affinity choline transporter CHT recycles choline back into synaptic terminals, which is the rate-limiting step to ACh production. CHT proteins traffic between the cell surface and subcellular organelles in a constitutive manner, which maintains plasma membrane transporter levels, thereby regulating CHT activity and maintaining cholinergic transmission. Pathological conditions associated with AD may alter CHT function in a manner that reduces choline uptake activity and impairs cholinergic neurotransmission. Thus, my …

Role Of Adaptor Trfa And Clppc In Controlling Levels Of Ssra-Tagged Proteins And Antitoxins In Staphylococcus Aureus, Niles P. Donegan, Jonathan S. Marvin, Ambrose L. Cheung

Dartmouth Scholarship

Staphylococcus aureus responds to changing extracellular environments in part by adjusting its proteome through alterations of transcriptional priorities and selective degradation of the preexisting pool of proteins. In Bacillus subtilis, the proteolytic adaptor protein MecA has been shown to play a role in assisting with the proteolytic degradation of proteins involved in competence and the oxidative stress response. However, the targets of TrfA, the MecA homolog in S. aureus, have not been well characterized. In this work, we investigated how TrfA assists chaperones and proteases to regulate the proteolysis of several classes of proteins in S. aureus. …

Targeting The Redox System To Overcome Mechanisms Of Drug Resistance In Chronic Lymphocytic Leukemia, Marcia A. Ogasawara

Dissertations & Theses (Open Access)

Chronic Lymphocytic Leukemia (CLL) is the most common form of leukemia diagnosed in Western countries and is characterized by clonal expansion of B cells. The clinical course of CLL is diverse and nearly 50% of patients present with chromosomal abnormalities. Deletion of the short arm on chromosome 17 (del17p) occurs in 5-7% of cases and presents with the shortest median survival time and often respond poorly to therapy. The tumor suppressor gene, TP53 is located on this region and it is well established that the p53 protein regulates multiple functions including: mitochondria biogenesis, response to DNA damage and redox balance. …

Antioxidant Gene Therapy Against Neuronal Cell Death, Juliana Navarro-Yepes, Laura Zavala-Flores, Anandhan Annadurai, Fang Wang, Maciej Skotak, Namas Chandra, Ming Li, Aglaia Pappa, Daniel Martinez-Fong, Luz Maria Del Razo, Betzabet Quintanilla-Vega, Rodrigo Franco

Department of Psychology: Faculty Publications

Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated inmitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. …

Heme Oxygenase-1 Induction Improves Cardiac Function Following Myocardial Ischemia By Reducing Oxidative Stress, Yossi Issan, Ran Kornowski, Dan Aravot, Asher Shainberg, Michal Laniado-Schwartzman, Komal Sodhi, Nader G. Abraham, Edith Hochhauser

Internal Medicine

Background

Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1), a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI) and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation.

Methods

In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP) and tin protoporphyrin (SnPP) prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers …

Therapeutic Implications Of Estrogen For Cerebral Vasospasm And Delayed Cerebral Ischemia Induced By Aneurysmal Subarachnoid Hemorrhage., Dale Ding, Robert M Starke, Aaron S Dumont, Gary K Owens, David M Hasan, Nohra Chalouhi, Md, Ricky Medel, Chih-Lung Lin

Department of Neurosurgery Faculty Papers

Cerebral vasospasm (CV) remains the leading cause of delayed morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). However, increasing evidence supports etiologies of delayed cerebral ischemia (DCI) other than CV. Estrogen, specifically 17 β -estradiol (E2), has potential therapeutic implications for ameliorating the delayed neurological deterioration which follows aneurysmal SAH. We review the causes of CV and DCI and examine the evidence for E2-mediated vasodilation and neuroprotection. E2 potentiates vasodilation by activating endothelial nitric oxide synthase (eNOS), preventing increased inducible NOS (iNOS) activity caused by SAH, and decreasing endothelin-1 production. E2 provides neuroprotection by increasing thioredoxin expression, decreasing c-Jun N-terminal …

Absence Of Manganese Superoxide Dismutase Delays P53-Induced Tumor Formation., Adam J. Case, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: Manganese superoxide dismutase (MnSOD) is a mitochondrial antioxidant enzyme that is down-regulated in a majority of cancers. Due to this observation, as well as MnSOD's potent antioxidant enzymatic activity, MnSOD has been suggested as a tumor suppressor for over 30 years. However, testing this postulate has proven difficult due to the early post-natal lethality of the MnSOD constitutive knock-out mouse. We have previously used a conditional tissue-specific MnSOD knock-out mouse to study the effects of MnSOD loss on the development of various cell types, but long-term cancer development studies have not been performed. We hypothesized the complete loss of …

Importance Of Bacillithiol In The Oxidative Stress Response Of Staphylococcus Aureus, Ana C. Posada, Stacey L. Kolar, Renata G. Dusi, Patrica Francois

Dartmouth Scholarship

In Staphylococcus aureus, the low-molecular-weight thiol called bacillithiol (BSH), together with cognate S-transferases, is believed to be the counterpart to the glutathione system of other organisms. To explore the physiological role of BSH in S. aureus, we constructed mutants with the deletion of bshA (sa1291), which encodes the glycosyltransferase that catalyzes the first step of BSH biosynthesis, and fosB (sa2124), which encodes a BSH-S-transferase that confers fosfomycin resistance, in several S. aureus strains, including clinical isolates. Mutation of fosB or bshA caused a 16- to 60-fold reduction in fosfomycin resistance in these S. aureus strains. High-pressure liquid chromatography analysis, which …

The Effects Of Dihydrobiopterin And Tetrahydrobiopterin On Hydrogen Peroxide And Nitric Oxide Release During Extracorporeal Shockwave Lithotripsy (Eswl), Brittany Deiling

PCOM Biomedical Studies Student Scholarship

ESWL is an effective, non-invasive therapy utilized to fragment stones in the kidney and subsequently be cleared in the urinary tract. Although lithotripsy provides a safer alternative to invasive treatments for removing stones, ESWL may cause vasoconstriction after ESWL treatment, reducing renal blood flow, which can cause kidney damage leading to acute to chronic hypertension clinically. This may be due to kidney vascular endothelial dysfunction, which is characterized as increased oxidative stress and decreased endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) bioavailability. We hypothesized that ESWL would decrease NO and increase hydrogen peroxide (H₂O₂) in …

Effects Of Short-Term Hyperglycemia On The Vasoconstriction Of The Aorta, Soner Dönmez, Osman Gökalp, Mustafa Doğan, Hüseyi̇n Vural, Barbaros Yi̇ği̇t

Turkish Journal of Medical Sciences

To investigate vasoconstrictor responses of healthy blood vessels to short-term hyperglycemic conditions such as postprandial hyperglycemia, gestational diabetes mellitus, and steroid-induced diabetes. Materials and methods: Female Wistar rat aorta rings were incubated in normal (11 mM) and high (22 mM and 44 mM) glucose concentrations for 4 h. Responses of vasoconstriction were measured in reaction to serotonin (10-5 M), phenylephrine (10-6 M), and KCl (60 mM) compared to the ambient condition, including different glucose concentrations. Results: While the responses of vasoconstriction to KCl were increased in the presence of Krebs' solution with high glucose, no statistically significant changes were observed …

Association Analyses Of Oxidative Stress, Aerobic Capacity, Daily Physical Activity, And Body Composition Parameters In Patients With Mild To Moderate Copd, Abdurrahman Genç, Kağan Üçok, Ümi̇t Şener, Tülay Koyuncu, Olcay Akar, Sefa Çeli̇k, Mehmet Ünlü

Turkish Journal of Medical Sciences

To investigate total oxidant and antioxidant status, maximal aerobic capacity, daily physical activity, pulmonary functions, and body composition changes, as well as the associations among these parameters, in patients with mild to moderate chronic obstructive pulmonary disease (COPD) versus healthy controls. Materials and methods: The study included 30 male patients newly diagnosed with COPD and 30 body mass index-matched, nonsmoker male controls. Maximal aerobic capacity, daily physical activity, total oxidant and antioxidant status, pulmonary function tests, body composition, and anthropometric parameters were measured. Results: Maximal aerobic capacity and total antioxidant values were lower in patients with COPD compared to the …

Effects Of Ozone Therapy And Taurine On Ischemia/Reperfusion-Induced Testicular Injury In A Rat Testicular Torsion Model, Tolga Reşat Aydos, Mehmet Murad Başar, Oğuz Kul, Hasan Tarik Atmaca, Tuba Uzunali̇oğlu, Üçler Kisa, Oğuzhan Eki̇n Efe

Turkish Journal of Medical Sciences

To investigate the effect of ozone and/or taurine treatment comparatively on testicular damage due to ischemia/reperfusion (I/R) injury in an experimental torsion model in rats. Materials and methods: Adult Wistar rats with and without torsion/detorsion were used. In order to monitor the effect of ozone and/or taurine treatment on testicular damage due to I/R injury, following histopathological investigation apoptotic indexes were scored by TUNEL method. Moreover, tumor necrosis factor receptor 1 (TNFR1), caspase 3, caspase 8, endothelial nitric oxide synthase (eNOS), tumor necrosis factor alpha (TNF\alpha), and cytochrome C immunostainings were performed and the levels of malondialdehyde, glutathione peroxidase, superoxide …

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 …