Life Sciences Commons^™

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 …

Effect Of Hydrogen Peroxide On The Biosynthesis Of Heme And Proteins: Potential Implications For The Partitioning Of Glu-TrnaGlu Between These Pathways, Carolina Farah, Gloria Levicán, Michael Ibba, Omar Orellana

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Glutamyl-tRNA (Glu-tRNA^Glu) is the common substrate for both protein translation and heme biosynthesis via the C5 pathway. Under normal conditions, an adequate supply of this aminoacyl-tRNA is available to both pathways. However, under certain circumstances, Glu-tRNA^Glu can become scarce, resulting in competition between the two pathways for this aminoacyl-tRNA. In Acidithiobacillus ferrooxidans, glutamyl-tRNA synthetase 1 (GluRS1) is the main enzyme that synthesizes Glu-tRNA^Glu. Previous studies have shown that GluRS1 is inactivated in vitro by hydrogen peroxide (H₂O₂). This raises the question as to whether H₂O₂ negatively affects …

An Active Role For The Ribosome In Determining The Fate Of Oxidized Mrna, Carrie L. Simms, Benjamin H. Hudson, John W. Mosior, Ali S. Rangwala, Hani S. Zaher

Biology Faculty Publications & Presentations

Chemical damage to RNA affects its functional properties and thus may pose a significant hurdle to the translational apparatus; however, the effects of damaged mRNA on the speed and accuracy of the decoding process and their interplay with quality-control processes are not known. Here, we systematically explore the effects of oxidative damage on the decoding process using a well-defined bacterial in vitro translation system. We find that the oxidative lesion 8-oxoguanosine (8-oxoG) reduces the rate of peptide-bond formation by more than three orders of magnitude independent of its position within the codon. Interestingly, 8-oxoG had little effect on the fidelity …

Selective Elimination Of Malignant Melanoma Using The Novel Anti-Tumor Agents, Osw-1 And Peitc, Kausar Begam Riaz Ahmed

Dissertations & Theses (Open Access)

Metastatic melanoma is amongst the most refractory of cancers. Drug resistance and lack of therapeutic selectivity are two main challenges to successful melanoma therapy. Herein, we investigated the mechanims of anticancer activity and therapeutic selectivity of two novel agents, 3β, 16β, 17α-trihydroxycholest-5-en-22-one 16-O-[2-O-4-methoxybenzoyl-β-D-xylopyranosyl]- [1→3]-2-O-acetyl-α-l-arabinopyranoside (OSW-1) and β-Phenylethyl Isothiocyanate (PEITC) in melanoma.

OSW-1 inhibited melanoma cell viability at nanomolar concentrations with minimal toxicity to normal melanocytes. Mechanistic studies revealed that OSW-1 suppressed Disialoganglioside 3 Synthase (GD3S) gene expression in melanoma cells, leading to inhibition of gangliosides GD3 and GD2. GD3 is an abundantly expressed melanoma …

Pregestational Diabetes And Congenital Heart Defects: Role Of Reactive Oxygen Species, Hoda Moazzen

Electronic Thesis and Dissertation Repository

Women with pregestational diabetes are at a high risk of having babies with congenital heart defects (CHDs). The mechanisms of CHD induction in the offspring of women with pregestational diabetes remain elusive. With an ever-increasing rate of diabetes in young adults, there is a pressing need to understand the underlying mechanisms and initiate effective preventative strategies. The aim of this thesis is to study the role of reactive oxygen species (ROS) signalling in heart morphogenesis, unravel molecular mechanisms of CHDs induced by pregestational diabetes and provide new insights on potential therapeutic strategies. To this end, a mouse model of pregestational …

Mechanistics Of Prothymosin Alpha And Nrf2 In The Keap1-Nrf2 Mediated Oxidative Stress Response, Halema Khan

Electronic Thesis and Dissertation Repository

In an effort to dissect the mechanism of interaction of IDPs, in this thesis we focus on Prothymosin a (ProTa) and nuclear factor erythroid 2-related factor 2 (Nrf2), intrinsically disordered proteins, in the Nrf2 mediated oxidative stress response. Kelch-like ECH-associated protein 1 (Keap1) is an inhibitor of Nrf2, a key transcription factor of cytoprotective genes. Under unstressed conditions, Keap1 interacts with Nrf2 in the cytoplasm via its Kelch domain and suppresses Nrf2 activity. During oxidative stress, Nrf2 is released from Keap1 and is shuttled to the nucleus, where it initiates pro cell survival gene transcription. ProTa also interacts with the …

Mitochondrial Involvement In Neuronal Cell Death, Josie J. Gray

Electronic Theses and Dissertations

Neuronal cell death via apoptosis or necrosis underlies several devastating neurodegenerative diseases associated with aging. Mitochondrial dysfunction resulting from oxidative or nitrosative stress often acts as an initiating stimulus for intrinsic apoptosis or necrosis. These events frequently occur in conjunction with imbalances in the mitochondrial fission and fusion equilibrium, although the cause and effect relationships remain elusive. In this thesis, I demonstrate in primary rat cerebellar granule neurons (CGNs) that oxidative or nitrosative stress induces an N-terminal cleavage of optic atrophy-1 (OPA1), a dynamin-like GTPase that regulates mitochondrial fusion and maintenance of cristae architecture. This cleavage event is indistinguishable from …

The Role Of Sirtuin Inhibitors On The Proteomic Responses Of The Mussels Mytilus Galloprovincialis And Mytilus Trossulus To Menadione Induced Oxidative Stress, Hayley C. Chilton

Master's Theses

Global climate change imposes physiological constraints on marine ecosystems that can alter the distribution of intertidal organisms. In one such instance, the native cold-adapted mussel Mytilus trossulus is being replaced along its southern range by the invasive warm-adapted Mytilus galloprovincialis. These blue mussels occur throughout rocky intertidal zones where they are subjected to greatly varying environmental conditions known to induce oxidative stress. We hypothesize that while under acute stress, related Mytilus congeners undergo a shift in redox potential from NADH-fueled respiratory pathways to pathways producing NADPH as a way to decrease the production of reactive oxygen species (ROS) and …

Understanding How Honey Bee Flight And Senescence Are Connected Through Oxidative Stress., Joseph Margotta

UNLV Theses, Dissertations, Professional Papers, and Capstones

The goal of this dissertation was to exploit the tractability of the honey bee (Apis mellifera) to understand how the physiological and cellular mechanisms that determine the onset and duration of senescence are shaped by behavioral development and behavioral intensity. These data reveal how behavior can damage cells and consequently limit lifespan. The honey bee represents the ideal model to address these factors because age, behavior, functional senescence, and lifespan are easily manipulated independently of each other while in its natural environment. I determined if there was a cause-effect relationship between honey bee flight and oxidative stress by comparing damage …

Transcriptional Activation Of Antioxidants May Compensate For Selenoprotein Deficiences In Amblyomma Maculatum (Acari: Ixodidae) Injected With Selk- Or Selm- Dsrna, S. Adamson, R. Browning, P. Singh, S. Nobles, A. Villareal, Shahid Karim

Faculty Publications

The Gulf‐Coast tick, Amblyomma maculatum, possesses an elaborate set of selenoproteins, which prevent the deleterious effects from oxidative stress that would otherwise occur during feeding. In the current work, we examined the role of selenoprotein K (SelK) and selenoprotein M (SelM) in feeding A. maculatum by bioinformatics, transcriptional gene expression, RNA interference and antioxidant assays. The transcriptional expression of SelK did not vary significantly in salivary glands or midguts throughout the bloodmeal. However, there was a 58‐fold increase in transcript levels of SelM in tick midguts. Ticks injected with selK‐dsRNA or selM‐dsRNA did not reveal any observable …

Redox Regulation Of Protein Translation In Eukaryotes, Maxim Gerashchenko

Department of Biochemistry: Dissertations, Theses, and Student Research

Gene expression may be controlled at multiple levels, e.g., through genomic architecture, transcription and translation. In the current work, we focused on regulation of protein synthesis. Historically, the investigation of the regulation of gene expression at the level of translation lagged behind the transcriptional control because of the lack of accessible high-throughput methods. Our research has begun with the finding of the use of alternative non-AUG start codon in thioredoxin-glutathione reductase (TGR), a selenoprotein involved in redox control during male reproduction. The use of this codon, CUG, relies on the Kozak consensus sequence and ribosomal scanning mechanism. However, the CUG …

A Lipid-Rich Gestational Diet Predisposes Offspring To Nonalcoholic Fatty Liver Disease: A Potential Sequence Of Events, Alexandria N. Hughes, Julia Thom Oxford

Biomolecular Research Center Publications and Presentations

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. It affects 20%–30% of the US population, and it is increasing worldwide. Recently, the role of lipid-rich maternal gestational nutrition in spurring the development of NAFLD among offspring has been indicated. Fetal predisposition to NAFLD involves numerous physiological reroutings that are initiated by increased delivery of nonesterified fatty acids to the fetal liver. Hampered ß-oxidation, uncontrolled oxidative stress, increased triacylglycerol synthesis, and the endoplasmic reticulum unfolded protein response are all implicated in sculpting a hepatic phenotype with a propensity to develop NAFLD in the postnatal state. This review …

Superoxide Signaling In Perivascular Adipose Tissue Promotes Age-Related Artery Stiffness, Bradley S. Fleenor, Jason S. Eng, Amy L. Sindler, Bryant T. Pham, Jackson D. Kloor, Douglas R. Seals

Graduate Center for Nutritional Sciences Faculty Publications

We tested the hypothesis that superoxide signaling within aortic perivascular adipose tissue (PVAT) contributes to large elastic artery stiffening in old mice. Young (4-6 months), old (26-28 months), and old treated with 4-Hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL), a superoxide scavenger (1 mm in drinking water for 3 weeks), male C57BL6/N mice were studied. Compared with young, old had greater large artery stiffness assessed by aortic pulse wave velocity (aPWV, 436 ± 9 vs. 344 ± 5 cm s(-1)) and intrinsic mechanical testing (3821 ± 427 vs. 1925 ± 271 kPa) (both P < 0.05). TEMPOL treatment in old reversed both measures of arterial stiffness. Aortic PVAT superoxide production was greater in old (P < 0.05 vs. Y), which was normalized with TEMPOL. Compared with young, old controls had greater pro-inflammatory proteins in PVAT-conditioned media (P < 0.05). Young recipient mice transplanted with PVAT from old compared with young donors for 8 weeks had greater aPWV (409 ± 7 vs. 342 ± 8 cm s(-1)) and intrinsic mechanical properties (3197 ± 647 vs. 1889 ± 520 kPa) (both P < 0.05), which was abolished with TEMPOL supplementation in old donors. Tissue-cultured aortic segments from old in the presence of PVAT had greater mechanical stiffening compared with old cultured in the absence of PVAT and old with PVAT and TEMPOL (both, P < 0.05). In addition, PVAT-derived superoxide was associated with arterial wall hypertrophy and greater adventitial collagen I expression with aging that was attenuated by TEMPOL. Aging or TEMPOL treatment did not affect blood pressure. Our findings provide evidence for greater age-related superoxide production and pro-inflammatory proteins in PVAT, and directly link superoxide signaling in PVAT to large elastic artery stiffness.

Assessment Of Neutrophil Functional Activity Following Prolonged Endurance Exercise, Katsuhiko Suzuki, Kaoru Sugama, Kayo Yoshitani, Koso Shiraishi, Takashi Kometani, Shigeki Miura, Hiroshi Yoshioka, Yuichi Mori

International Journal of Exercise Science: Conference Proceedings

Introduction: Neutrophils not only play an important role in host defense by migrating to the site of infection and producing reactive oxygen species (RO S), but also mediate pathological process in inflammatory tissue damage. Therefore, it is import ant not only to assess but also modulate neutrophil activities for disease prevention. We hav e reported that exhaustive exercise causes neutrophil priming (Suzuki et al. J. Appl. Physiol. , 81, 1213-1222, 1996) which might be associated wi th muscle damage (Suzuki et al. J. Appl. Physiol. , 87, 1360-1367, 1999), but antioxidant capacity is also activated following exercise (Suzuki et al. …

Assessment Of Neutrophil Functional Activity Following Prolonged Endurance Exercise, Katsuhiko Suzuki, Kaoru Sugama, Kayo Yoshitani, Koso Shiraishi, Takashi Kometani, Shigeki Miura, Hiroshi Yoshioka, Yuichi Mori

International Journal of Exercise Science: Conference Proceedings

ntroduction: Neutrophils not only play an important role in host defense by migrating to the site of infection and producing reactive oxygen species (RO S), but also mediate pathological process in inflammatory tissue damage. Therefore, it is import ant not only to assess but also modulate neutrophil activities for disease prevention. We hav e reported that exhaustive exercise causes neutrophil priming (Suzuki et al. J. Appl. Physiol. , 81, 1213-1222, 1996) which might be associated wi th muscle damage (Suzuki et al. J. Appl. Physiol. , 87, 1360-1367, 1999), but antioxidant capacity is also activated following exercise (Suzuki et al. …

Stress Adaptation In A Pathogenic Fungus, Alistair J. P. Brown, Susan Budge, Despoina Kaloriti, Anna Tillmann, Mette D. Jacobsen, Zhikang Yin, Iuliana V. Ene, Iryna Bohovych, Doblin Sandai, Stavroula Kastora, Joanna Potrykus, Elizabeth R. Ballou, Delma S. Childers, Shahida Shahana, Michelle D. Leach

Department of Biochemistry: Faculty Publications

Candida albicans is a major fungal pathogen of humans. This yeast is carried by many individuals as a harmless commensal, but when immune defences are perturbed it causes mucosal infections (thrush). Additionally, when the immune system becomes severely compromised, C. albicans often causes life-threatening systemic infections. A battery of virulence factors and fitness attributes promote the pathogenicity of C. albicans. Fitness attributes include robust responses to local environmental stresses, the inactivation of which attenuates virulence. Stress signalling pathways in C. albicans include evolutionarily conserved modules. However, there has been rewiring of some stress regulatory circuitry such that the roles of …

Environmental Stressors: Pathways Of Exposure And Aquatic Invertebrate Response, Carly Jean Nowicki

Wayne State University Dissertations

The need to monitor freshwater and detect impairments prior to observable impacts is crucial to maintain species diversity and ecosystem function. Therefore, understanding the contribution of various matrices (i.e., sediment and water) to chemical exposure is critical for remediation of impacted sites.

To evaluate various matrices of chemical exposure, I focused on the organic pollutant polychlorinated biphenyls (PCBs) due to their relatively ubiquitous nature, high toxicity, and adverse effects on humans and wildlife. In complementary laboratory and field experiments, I compared the effects of aqueous versus sedimentary exposure of PCBs on invertebrates. In the laboratory, organisms exposed to PCB-contaminated sediments …

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 …

Circadian Regulation Of Mtor Signaling Via Bmal1 Dependent Mechanism, Rohini Vishal Khapre

ETD Archive

Understanding mechanisms of aging is important for the treatment and prevention of age-associated pathologies. However, these mechanisms are not well understood. Recently we have demonstrated that the circadian clock (an internal time keeping system) regulates longevity in mammals, but the molecular mechanisms are not known. The aim of our current study is to investigate a possible interconnection between the circadian clock and mTORC1 (mammalian target of Rapamycin) signaling pathway. mTORC1 pathway is a nutrient response pathway involved in many cellular processes many recent studies indicate a role of mTORC1 pathway in aging. Here we demonstrate that circadian system regulates mTORC1 …

The Role Of Exercise In Polychlorinated Biphenyl Induced Cardiovascular Disease, Margaret O'Bryan Murphy

Theses and Dissertations--Nutritional Sciences

Cardiovascular disease remains the leading cause of death in Western societies. Endothelial dysfunction is one of the initiating steps in the development of atherosclerosis. While there is a strong correlation with a person’s genetics, lifestyle factors including smoking, physical activity, and diet can significantly increase a person’s susceptibility to the development of atherosclerosis. In addition to these lifestyle factors, there is a strong body of evidence linking exposure to environmental pollutants including persistent organic pollutants such as polychlorinated biphenyls to increased cardiovascular disease and mortality. It has been well-established that exercise protects against cardiovascular disease, but whether exercise can modulate …

A Preliminary Proteomic Evaluation Of Smooth Muscle Cells In Thoracic Aortic Aneurysms, Ceyda Açilan Ayhan, Betül Baykal, Müge Serhatli, Ömer Kaçar, Zelal Adigüzel, Serpi̇l Taş, Kemal Baysal, Ahmet Tarik Baykal

Turkish Journal of Biology

Aortic aneurysm is characterized as localized degeneration of the aorta leading to advanced weakening and widening of the vessel. While the exact mechanisms have yet to be determined, current studies indicate that the degradation of extracellular matrix (ECM) proteins and apoptosis of vascular smooth muscle cells (SMCs) may result in extendibility, dilation, and rupture of the vessel. Within the aortic wall, SMCs are implicated as key components involved in disease development, as numerous molecular changes have been reported to occur. Most current studies involve either investigation of proteins constituting a group or pathway in SMCs, or analyses of the whole …

Melatonin Is Effective In Reducing Stress-Induced Organ Damage In Wistar Albino Rats, Mukaddes Eşrefoğlu, Ayşi̇n Akinci Bak, Hülya Elbe, Eli̇f Taşlidere, Asli Çeti̇n, Burhan Ateş

Turkish Journal of Biology

In the present study, we tried to investigate the effects of melatonin, a novel antioxidant and a potent free radical scavenger, in stress-induced cerebral, cerebellar, cardiac, and hepatic oxidative damage using microscopic and biochemical analysis. A total of 32 male Wistar albino rats were divided into control, stress, stress + saline, and stress + melatonin groups. The rats from the stress groups were exposed to high stress conditions of starvation, immobilization, and cold exposure. The rats from the stress + melatonin group received melatonin daily at 20 mg/kg body weight intraperitoneally for 7 days. At the end of the experiment, …

Study Of Exogenous Oxidative Stress Response In Escherichia Coli, Pseudomonas Spp., Bacillus Spp., And Salmonella Spp., Ifratun Nur, Mohammad Sakil Munna, Rashed Noor

Turkish Journal of Biology

With a previous observation of Escherichia coli growth cessation with the supplementation of 3 mM hydrogen peroxide (H_{2}O_{2}) at the late log phase, the current study further demonstrated the consequences of the addition of an increased concentration (6 mM) of H_{2}O_{2} and further extended the investigation on such an oxidant's impact on the growth of Salmonella spp., Pseudomonas spp., and Bacillus spp. Cell culturability was measured through the enumeration of colony-forming units (CFUs) on agar plates for up to 72 h. Subsequent changes in cell morphology and arrangements were monitored, and the cell viability was simultaneously retraced by spot tests. …

It Takes 2 Antioxidants To Tango: The Interaction Between Manganese Superoxide Dismutase And Glutathione Peroxidase-1, Dede N. Ekoue, Alan M. Diamond

Turkish Journal of Biology

Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism. Accumulation of ROS without an effective antioxidant response can lead to oxidative stress, resulting in macromolecular damage that is implicated in the etiology of various diseases including cancer. ROS detoxification is regulated by various antioxidant proteins, specifically manganese superoxide dismutase (MnSOD), which catalyzes the conversion of superoxide into H_{2}O_{2}, and the subsequent conversion of H_{2}O_{2} into water is catalyzed by glutathione peroxidase 1 (GPx-1). In vitro and in vivo evidence supports a conflicting role of MnSOD in tumor biology and indicates that an interaction between MnSOD and GPx-1 can modulate …

A Functional Genomics Approach To Investigate The Mechanism Of Action Of The Histone Deacetylase Inhibitor Cg-1521, Ann-Christin Gaupel

Legacy Theses & Dissertations (2009 - 2024)

Epigenetic alterations are common in human cancers. Loss of histone acetylation occurs early in tumorigenesis, correlates with advanced stage and poor clinical outcome, and histone acetyltransferases (HATs) and histone deacetylases (HDACs) are aberrantly expressed or recruited to promoters in a variety of cancers. Histone deacetylase inhibitors (HDACis) are attractive anti-cancer therapeutics because of their selectivity for transformed cells and their ability to induce growth arrest, cell death, senescence and differentiation, enhance tumor immunogenicity and inhibit angiogenesis and invasion. However, many questions remain regarding their mechanism(s) of action. While monotherapy with HDACis for solid tumors is not effective, combination therapies show …

Cancer Chemopreventive Effect Of Dietary Zataria Multiflora Essential Oils, Abolfazl Dadkhah, Faezaeh Fatemi, Mohammad Reza Mohammadi Malayeri, Azadeh Rasooli

Turkish Journal of Biology

Zataria multiflora Boiss., with the common name Avishan-e-Shirazi, is native to Iran. This herb has been found to possess varied pharmacological properties. In the present study, for the first time, colon chemopreventive effects of Z. multiflora essential oils (0.01% and 0.1% in the diet) in rats treated with 1,2-dimethylhydrazine (DMH) were demonstrated. For this purpose, the oxidative stress/antioxidant parameters (lipid peroxidation, glutathione, superoxide dismutase, catalase, and ferric reducing ability of plasma) concomitant with xenobiotic metabolizing enzymes (CYP450 and GST) were considered. Moreover, the colonic Beta-catenin protein was examined in colon tissues followed by histopathological analysis. The results showed that the …

Increase Of Basal Oxidative Stress Levels And Impairment Of Heme Oxygenase-1/Biliverdin Reductase Post-Translational Modification By The Defect Of Parkinson-Related Gene Of Pink1, Zhaoshu Zhang

Theses and Dissertations--Chemistry

Parkinson disease (PD) is the most common movement disorder and the second most common neurodegenerative disease. PINK1, PTEN-induced kinase 1, functions as a serine/threonine kinase as well as a protector of mitochondrial function. Mutations in PINK1 gene result in either mitochondria dysfunction or disruption of kinase signaling pathways involved in the pathogenesis of PD.

In this thesis, oxidative stress levels were examined in the brain of PINK1 knockout mice, and also how heme oxygenase-1 and biliverdin reductase are affected in brain of PINK1 knockout mice. In addition, posttranslational modifications are a way to control the behavior of proteins, so posttranslational …

Addressing Public Health Risks Of Persistent Pollutants Through Nutritional Modulation And Biomimetic Nanocomposite Remediation Platforms, Bradley J. Newsome

Theses and Dissertations--Chemistry

Due to their relative chemical stability and ubiquity in the environment, chlorinated organic contaminants such as polychlorinated biphenyls (PCBs) pose significant health risks and enduring remediation challenges. Engineered nanoparticles (NPs) provide a novel platform for sensing/remediation of these toxicants, in addition to the growing use of NPs in many industrial and biomedical applications, but there remains concern for their potential long-term health effects. Research highlighted herein also represents a transdisciplinary approach to address human health challenges associated with exposure to PCBs and NPs. The objectives of this dissertation research are two-fold, 1) to develop effective methods for capture/sensing and remediation …