Medicine and Health Sciences Commons^™

Novel Method For The High-Throughput Processing Of Slides For The Comet Assay, Mahsa Karbaschi, Marcus Cooke

Dr. Marcus S. Cooke PhD, FRCPath

Single cell gel electrophoresis (the comet assay), continues to gain popularity as a means of assessing DNA damage. However, the assay’s low sample throughput and laborious sample workup procedure are limiting factors to its application. “Scoring”, or individually determining DNA damage levels in 50 cells per treatment, is time-consuming, but with the advent of high-throughput scoring, the limitation is now the ability to process significant numbers of comet slides. We have developed a novel method by which multiple slides may be manipulated, and undergo electrophoresis, in batches of 25 rather than individually and, importantly, retains the use of standard microscope …

Translocation Of Cyclin C During Oxidative Stress Is Regulated By Interactions With Multiple Trafficking Proteins, Daniel G J Smethurst, Katrina F Cooper, Randy Strich

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Eukaryotic cells take cues from their environment and interpret them to enact a response. External stresses can produce a decision between adjusting to behaviors which promote surviving the stress, or enacting a cell death program. The decision to undergo programmed cell death (PCD) is controlled by a complex interaction between nuclear and mitochondrial signals. The mitochondria are highly dynamic organelles that constantly undergo fission and fusion. However, a dramatic shift in mitochondrial morphology toward fission occurs early in the PCD process. We have identified the transcription factor cyclin C as the biochemical trigger for stress‐induced mitochondrial hyper‐fragmentation in yeast (Cooper …

Snf1 Dependent Destruction Of Med13 Is Required For Programmed Cell Death Following Oxidative Stress In Yeast, Stephen D Willis, David C Stieg, R. Shah, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

All eukaryotic cells, when faced with unfavorable environmental conditions, have to decide whether to mount a survival or cell death response. The conserved cyclin C and its kinase partner Cdk8 play a key role in this decision. Both are members of the Cdk8 kinase module that, along with Med12 and Med13, associate with the core mediator complex of RNA polymerase II. In S. cerevisiae, oxidative stress triggers Med13 destruction¹, which thereafter releases cyclin Ci nto the cytoplasm. Cytoplasmic cyclin C associates with mitochondria where it induces hyper-fragmentation and programmed cell death². This suggests a model in …

Modification Of The Ribosome As Part Of The Adaptive Response To Oxidative Stress In Yeast, Jessica A Zinskie, Daniel Shedlovskiy, Ethan Gardner, Dimitri G Pestov, Natalia Shcherbik

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Living organisms are constantly exposed to a variety of environmental and internal stressors tha tare detrimental to their cellular physiology and viability. One such condition, oxidativestress, is caused by abnormal amounts of Reactive Oxygen Species (ROS) that can lead to damage to proteins, nucleic acids, and lipids. Although the mechanisms to neutralize ROS have been widely studied, the understanding of ROS‐mediated signaling for these mechanisms is rather incomplete and sparse. We have uncovered a previously undescribed phenomenon of yeast ribosomes to respond to elevated levels of ROS through a specific endonucleolytic cleavage of the 25S rRNA in the c‐loop of …

Elevated Dna Oxidation And Dna Repair Enzyme Expression In Brain White Matter In Major Depressive Disorder, Attila Szebeni, Katalin Szebeni, Timothy P. Diperi, Luke A. Johnson, Craig A. Stockmeier, Jessica D. Crawford, Michelle J. Chandley Health Sciences, Liza J. Hernandez, Katherine C. Burgess, Russell W. Brown, Gregory A. Ordway

Russell W. Brown

Background: Pathology of white matter in brains of patients with major depressive disorder (MDD) is well-documented, but the cellular and molecular basis of this pathology are poorly understood.

Methods:Levels of DNA oxidation and gene expression of DNA damage repair enzymes were measured in Brodmann area 10 (BA10) and/or amygdala (uncinate fasciculus) white matter tissue from brains of MDD (n=10) and psychiatrically normal control donors (n=13). DNA oxidation was also measured in BA10 white matter of schizophrenia donors (n=10) and in prefrontal cortical white matter from control rats (n=8) and rats with repeated stress-induced anhedonia (n=8).

Results:DNA oxidation …

Mitochondrial Reactive Oxygen Species In Lipotoxic Hearts Induces Post-Translational Modifications Of Akap121, Drp1 And Opa1 That Promote Mitochondrial Fission, Kensuke Tsushima, Heiko Bugger, Adam R. Wende, Jamie Soto, Gregory A. Jenson, Austin R. Tor, Rose Mcglauflin, Helena C. Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X. Hu, Crystal L. Sloan, Renata O. Pereira, Vitor A. Lira, Kenneth W. Spitzer, Terry L. Sharp, Kooresh I. Shoghi, Genevieve C. Sparagna, Eva A. Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E. Schaffer, E. Dale Abel

Department of Biochemistry: Faculty Publications

Rationale: Cardiac lipotoxicity, characterized by increased uptake, oxidation and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood.

Objective: To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo.

Methods and Results: Using a transgenic mouse model of cardiac lipotoxicity overexpressing long-chain acyl-CoA synthetase 1 in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter. This is associated with increased palmitoyl-carnitine oxidation and increased reactive oxygen species (ROS) generation …

Effect Of Carbon Monoxide-Releasing Molecule-3 On The Severity Of Endothelial Dysfunction Due To Elevation Of Hydrostatic Pressure In An In Vitro Model Of Compartment Syndrome, Michel A. Taylor

Electronic Thesis and Dissertation Repository

Compartment syndrome (CS) is a surgical emergency caused by elevated pressure within a closed osseofascial compartment. It leads to microvascular dysfunction, limiting oxygen and nutrient delivery, gas exchange, resulting in cellular anoxia, muscle necrosis and cell death.

Currently, the only effective treatment is surgical fasciotomy. Recently, carbon monoxide (CO) delivered via carbon monoxide releasing molecule-3 (CORM-3) has been shown to improve microvascular perfusion and convey anti-inflammatory benefits in animal models of CS.

The contribution of elevated hydrostatic pressure (EHP) to the pathophysiology of CS was examined in an in vitro model of CS. We found that EHP led to increased …

Acute Maternal Oxidant Exposure Causes Susceptibility Of The Fetal Brain To Inflammation And Oxidative Stress, Feroz Akhtar, Christopher A. Rouse, Gabriel Catano, Marcus Montalvo, Sarah L. Ullevig, Reto Asmis, Kusum Kharbanda, Shivani K. Maffi

School of Medicine Publications and Presentations

Background

Maternal exposure to environmental stressors poses a risk to fetal development. Oxidative stress (OS), microglia activation, and inflammation are three tightly linked mechanisms that emerge as a causal factor of neurodevelopmental anomalies associated with prenatal ethanol exposure. Antioxidants such as glutathione (GSH) and CuZnSOD are perturbed, and their manipulation provides evidence for neuroprotection. However, the cellular and molecular effects of GSH alteration in utero on fetal microglia activation and inflammation remain elusive.

Methods

Ethanol (EtOH) (2.5 g/kg) was administered to pregnant mice at gestational days 16–17. One hour prior to ethanol treatment, N-acetylcysteine (NAC) and L-buthionine sulfoximine (BSO) …

Chemotherapy-Induced Tissue Injury: An Insight Into The Role Of Extracellular Vesicles-Mediated Oxidative Stress Responses, Chontida Yarana, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

The short- and long-term side effects of chemotherapy limit the maximum therapeutic dose and impair quality of life of survivors. Injury to normal tissues, especially chemotherapy-induced cardiomyopathy, is an unintended outcome that presents devastating health impacts. Approximately half of the drugs approved by the Food and Drug Administration for cancer treatment are associated with the generation of reactive oxygen species, and Doxorubicin (Dox) is one of them. Dox undergoes redox cycling by involving its quinone structure in the production of superoxide free radicals, which are thought to be instrumental to the role it plays in cardiomyopathy. Dox-induced protein oxidation changes …

Enhanced Physical Endurance And Improved Memory Performance Following Taurine Administration In Rats, Irfan Sajid, Saara Muddasir, Shaista Emad, Zehra Batool, Saima Khaliq, Lubna Anis, Saiqa Tabassum, Syeda Madiha, Laraib Liaquat, Sadia Sadir, Tahira Perveen, Saida Haider

Department of Biological & Biomedical Sciences

Energy drinks enhance physical endurance and cognitive ability. The ingredients present in these drinks are considered as ergogenic and have memory boosting effects. In the present study effects of taurine administration for one week was monitored on physical exercise and memory performance in rats. Animals were divided into two groups namely control and test. Taurine was injected intraperitoneally to the test group at the dose of 100mg/kg. After one week of treatment rats were subjected to physical exercise and memory task. Results of this study revealed that rats injected with taurine for one week exhibited improved muscular strength as well …

Targeting Antioxidant Enzyme Expression As A Therapeutic Strategy For Ischemic Stroke, Stephanie M. Davis, Keith R. Pennypacker

Center for Advanced Translational Stroke Science Faculty Publications

During ischemic stroke, neurons and glia are subjected to damage during the acute and neuroinflammatory phases of injury. Production of reactive oxygen species (ROS) from calcium dysregulation in neural cells and the invasion of activated immune cells are responsible for stroke-induced neurodegeneration. Scientists have failed thus far to identify antioxidant-based drugs that can enhance neural cell survival and improve recovery after stroke. However, several groups have demonstrated success in protecting against stroke by increasing expression of antioxidant enzymes in neural cells. These enzymes, which include but are not limited to enzymes in the glutathione peroxidase, catalase, and superoxide dismutase families, …

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Jiang Liu

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice fed …

Elevated Dna Oxidation And Dna Repair Enzyme Expression In Brain White Matter In Major Depressive Disorder, Attila Szebeni, Katalin Szebeni, Timothy P. Diperi, Luke A. Johnson, Craig A. Stockmeier, Jessica D. Crawford, Michelle J. Chandley Health Sciences, Liza J. Hernandez, Katherine C. Burgess, Russell W. Brown, Gregory A. Ordway

ETSU Faculty Works

Background: Pathology of white matter in brains of patients with major depressive disorder (MDD) is well-documented, but the cellular and molecular basis of this pathology are poorly understood.

Methods:Levels of DNA oxidation and gene expression of DNA damage repair enzymes were measured in Brodmann area 10 (BA10) and/or amygdala (uncinate fasciculus) white matter tissue from brains of MDD (n=10) and psychiatrically normal control donors (n=13). DNA oxidation was also measured in BA10 white matter of schizophrenia donors (n=10) and in prefrontal cortical white matter from control rats (n=8) and rats with repeated stress-induced anhedonia (n=8).

Results:DNA oxidation …

Short-Term Bilateral Adrenalectomy: Biochemical And Morphological Alterations In The Rat Hippocampus, Ahlam Said Abi Issa

Theses

Several studies showed the effects of glucocorticoid hormones on the hippocampus. It has been reported that the chronic administration of high dose glucocorticoids (GC) results in the degeneration of pyramidal neurons. However, bilateral adrenalectomy has been shown to damage the hippocampal neurons. Although the effects of long-term adrenalectomy have been studied extensively, there are few publications on the effects of short-term bilateral adrenalectomy (ADX). We aimed to investigate the effects of ADX on levels of pro-inflammatory cytokines interleukin-1β (IL-1β), interkeukin-6 (IL-6) and tumor necrosis factor-α (TNF-α); levels of growth factors, response of microglia and astrocytes to neuronal death, and oxidative …

Biochemical And Histopathological Changes In The Brain Of Albino Rats Treated With Profenofos And The Possible Protective Effect Of Vitamins C And E, Amira M. El-Seidy, Safaa A. Amine, Samy M. Badawy, Samy A. Hammad, Shireen R. Abdou Slima

Menoufia Medical Journal

Objective The aim of this study was to evaluate the changes in the brain of albino rats treated with profenofos and the possible protective effect of vitamins C and E against the acute effect of profenofos. Background During the last decades the use of pesticides has increased steadily in developing countries in an effort to increase food production and control vector-borne diseases in plants. Organophosphorus (OP) compounds are widely used in agriculture as insecticides. OP poisoning is common due to its wide availability. Profenofos is a widely used insecticide and has been classified as moderately hazardous. OP pesticides are known …

Neurovascular Unit Dysfunction And Blood-Brain Barrier Hyperpermeability Contribute To Schizophrenia Neurobiology: A Theoretical Integration Of Clinical And Experimental Evidence, S. Najjar, S. Pahlajani, V. De Sanctis, J. N.H. Stern, A. Najjar, D. Chong

Journal Articles

No abstract provided.

Effects Of Massive Ovulation On Oxidation State And Function Of The Ovaries In Laying Hens, Yu Chang, Jinghai Feng, Minhong Zhang, Liwen Jiang, Lili Zhai, Xiaolan Yang

Turkish Journal of Veterinary & Animal Sciences

Modern laying hens show fast reduction in egg production rate after 60 weeks of age, which is associated with the decline in ovarian function. The aim of this study was to examine the influence of massive ovulation on the oxidation state and ovarian function in hens. In total, 48 Jing Hong hens aged 17 weeks were randomly divided into high ovulation (HO) and low ovulation (LO) groups. The LO hens were exposed to 6 h of light per day (6 L:18 D) up to 32 weeks to delay the initiation of egg production and then were switched to 16 L:8 …

Tenofovir Induced Nephrotoxicity: A Mechanistic Study, Rachel A. Murphy

Theses, Dissertations and Capstones

Tenofovir (TFV) is a reverse transcriptase inhibitor that is approved by the United States Food and Drug Administration (FDA) to treat HIV and chronic Hepatitis B. It has a long half-life, allowing for once a day dosing and is effective in treatment of both naive and experienced patients. It is administered orally as tenofovir disoproxil fumarate (TDF) and is deesterified in plasma to the active drug TFV. However, renal impairment is associated with its use; TFV can induce decreased glomerular filtration rate (GFR) and free calcitriol, renal failure, and Fanconi Syndrome. The exact mechanism of toxicity currently remains unknown, largely …

On The Origin Of Superoxide Dismutase: An Evolutionary Perspective Of Superoxide-Mediated Redox Signaling., Adam J. Case

Journal Articles: Cellular & Integrative Physiology

The field of free radical biology originated with the discovery of superoxide dismutase (SOD) in 1969. Over the last 5 decades, a plethora of research has been performed in species ranging from bacteria to mammals that has elucidated the molecular reaction, subcellular location, and specific isoforms of SOD. However, while humans have only begun to study this class of enzymes over the past 50 years, it has been estimated that these enzymes have existed for billions of years, and may be some of the original enzymes found in primitive life. As life evolved over this expanse of time, these enzymes …

Cellular And Molecular Mechanisms Underlying Alcohol-Induced Aggressiveness Of Breast Cancer, Yongchao Wang, Mei Xu, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Breast cancer is a leading cause of morbidity and mortality in women. Both Epidemiological and experimental studies indicate a positive correlation between alcohol consumption and the risk of breast cancer. While alcohol exposure may promote the carcinogenesis or onset of breast cancer, it may as well enhance the progression and aggressiveness of existing mammary tumors. Recent progress in this line of research suggests that alcohol exposure is associated with invasive breast cancer and promotes the growth and metastasis of mammary tumors. There are multiple potential mechanisms involved in alcohol-stimulated progression and aggressiveness of breast cancer. Alcohol may increase the mobility …

The Potential Role Of Oxidative Stress In Reduced Uterine Perfusion Pressure Vascular Reactivity, Abigail J. Gindlesberger

Williams Honors College, Honors Research Projects

Preeclampsia is a hypertensive disease of pregnant women that is known to cause detrimental physiological complications to both the mother and fetus. The hypertension hypothesized to result from endothelial dysfunction may be improved therapeutically by increasing Vascular Endothelial Growth Factor ligand concentration and it’s Vascular Endothelial Growth Factor Receptor 2 (VEGF and VEGFR2). Together, this receptor pathway may help overall vasodilation of key blood vessels linking the mother and fetal placental unit, allowing for increased clinical pathologies of both. Previous studies have also linked increased reactive oxygen species (ROS) production in preeclamptic pregnancies to the damaged endothelial tissues of the …

Relationship Between Selected Micronutrient Deficiencies And Oxidative Stress Biomarkers In Diabetes Mellitus Patients With Foot Ulcers In Ibadan, Nigeria, Elizabeth Bosede Bolajoko, Olubayo Michael Akinosun, John Anetor, Kensese Sontin Mossanda

Turkish Journal of Medical Sciences

Background/aim: Micronutrients are indispensable in the prevention of diseases and maintenance of good health. Their deficiencies have been implicated in several diseases associated with oxidative stress (OS). This study aimed at investigating the levels of some vitamins and minerals in association with OS markers in diabetic foot ulcer (DFU) patients in Ibadan, Oyo State, Nigeria. Materials and methods: Seventy DFU patients and 50 apparently healthy volunteers (controls) were recruited for the study. Blood samples of 10 mL were collected after a 10-h overnight fast from each participant after obtaining their consent. Levels of oxidative stress biomarkers such as lipid peroxide …

The Role Of Oxidative Stress In α-Amanitin-Induced Hepatotoxicityin An Experimental Mouse Model, Zerri̇n Defne Dündar, Mehmet Ergi̇n, İbrahi̇m Kilinç, Tamer Çolak, Pembe Oltulu, Başar Cander

Turkish Journal of Medical Sciences

Background/aim: This study aimed to evaluate oxidative stress markers of liver tissue in a mouse α-amanitin poisoning model with three different toxin levels. Materials and methods: The mice were randomly divided into Group 1 (control), Group 2 (0.2 mg/kg), Group 3 (0.6 mg/kg), and Group 4 (1.0 mg/kg). The toxin was injected intraperitoneally and 48 h of follow-up was performed before sacrifice. Results: Median superoxide dismutase activities of liver tissue in Groups 3 and 4 were significantly higher than in Group 1 (for both, P = 0.001). The catalase activity in Group 2 was significantly higher, but in Groups 3 …

Antioxidants Status In Type 2 Diabetic Patients In Morocco, Rachid Eljaoudi, Naoual Elomri, Meryem Laamarti, Yahia Cherrah, Taoufik Amezyane, Driss Ghafir, Azeddine Ibrahimi

Turkish Journal of Medical Sciences

Background/aim: Type 2 diabetes is a heterogeneous and multifactorial metabolic disorder with some relationship to oxidative stress (OS). Since no studies were conducted in the Moroccan population, this clinical investigation aimed at evaluating the antioxidants status in Moroccan patients with type 2 diabetes. Materials and methods: Blood samples of 60 type 2 diabetic patients and 40 healthy controls subjects were analyzed for determination of glycemia, hemoglobin, CRP, glycated hemoglobin, lipid parameters, malondialdehyde (MDA), vitamins E and C, copper (Cu), zinc (Zn), and selenium (Se). Results: CRP and triglycerides were higher in the diabetic group while high-density lipoprotein levels were significantly …

Vitamin E As A Novel Therapy In The Treatment Of Acute Aluminum Phosphide Poisoning, Zahra Halvaei, Hiva Tehrani, Kambiz Soltaninejad, Mohammad Abdollahi, Shahin Shadnia

Turkish Journal of Medical Sciences

Background/aim: Aluminum phosphide (AlP) is commonly used as a fumigant in developing countries. Induction of oxidative stress is one of the most important mechanisms of its toxicity. In this regard, and considering that there is no specific antidote for its treatment, the aim of this study was to evaluate the effect of vitamin E in the treatment of acute AlP poisoning. Materials and methods: This was a clinical trial on acute AlP poisoned patients. All patients received supportive treatment. In addition, the treatment group received vitamin E (400 mg/BD/IM). Level of malondialdehyde (MDA) and total antioxidant capacity of plasma were …