Medicine and Health Sciences Commons^™

Apigenin Alleviates Autistic-Like Stereotyped Repetitive Behaviors And Mitigates Brain Oxidative Stress In Mice, Petrilla Jayaprakash, Dmytro Isaev, Keun-Hang Susan Yang, Rami Beiram, Murat Oz, Bassem Sadek

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder (ASD) has gained a growing interest. The flavonoid apigenin (APG) has been confirmed in its pharmacological action as a positive allosteric modulator of α7-nAChRs. However, there is no research describing the pharmacological potential of APG in ASD. The aim of this study was to evaluate the effects of the subchronic systemic treatment of APG (10–30 mg/kg) on ASD-like repetitive and compulsive-like behaviors and oxidative stress status in the hippocampus and cerebellum in BTBR mice, utilizing the reference drug aripiprazole (ARP, 1 …

Oxidative Stress And Ion Channels In Neurodegenerative Diseases, Razan Orfali, Adnan Z. Alwatban, Rawan S. Orfali, Liz Lau, Noble Chea, Abdullah M. Alotaibi, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson’s, Alzheimer’s, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington’s disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly …

Invasive Frogs Show Persistent Physiological Differences To Elevation And Acclimate To Colder Temperatures, Jack R. Marchetti, Karen H. Beard, Emily E. Virgin, Erin L. Lewis, Steven C. Hess, Kwanho C. Ki, Layne O. Sermersheim, Adriana P. Furtado, Susannah S. French

USDA Wildlife Services: Staff Publications

The coqui frog (Eleutherodactylus coqui) was introduced to the island of Hawai’i in the 1980s and has spread across much of the island. Concern remains that this frog will continue to expand its range and invade higher elevation habitats where much of the island’s endemic species are found. We determined whether coqui thermal tolerance and physiology change along Hawai’i’s elevational gradients. We measured physiological responses using a short-term experiment to determine baseline tolerance and physiology by elevation, and a long-term experiment to determine the coqui’s ability to acclimate to different temperatures. We collected frogs from low, medium, and high elevations. …

Potential Of Synthetic And Natural Compounds As Novel Histone Deacetylase Inhibitors For The Treatment Of Hematological Malignancies, Dilipkumar Pal, Khushboo Raj, Shyam Sundar Nandi, Surajit Sinha, Abhishek Mishra, Arijit Mondal, Ricardo Lagoa, Jack T. Burcher, Anupam Bishayee

Journal Articles: Cellular & Integrative Physiology

Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are enzymes that remove or add acetyl groups to lysine residues of histones, respectively. Histone deacetylation causes DNA to more snugly encircle histones and decreases gene expression, whereas acetylation has the opposite effect. Through these small alterations in chemical structure, HATs and HDACs regulate DNA expression. Recent research indicates histone deacetylase inhibitors (HDACis) may be used to treat malignancies, including leukemia, B-cell lymphoma, virus-associated tumors, and multiple myeloma. These data suggest that HDACis may boost the production of immune-related molecules, resulting in the growth of CD8-positive T-cells and the recognition of nonreactive tumor …

Oxidative Stress Strongly Restricts The Effect Of Codon Choice On The Efficiency Of Protein Synthesis In Escherichia Coli, Lorenzo Eugenio Leiva, Sara Elgamal, Sebastian A. Leidel, Omar Orellana, Michael Ibba, Assaf Katz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Introduction

The response of enterobacteria to oxidative stress is usually considered to be regulated by transcription factors such as OxyR and SoxR. Nevertheless, several reports have shown that under oxidative stress the levels, modification and aminoacylation of tRNAs may be altered suggesting a role of codon bias in regulation of gene expression under this condition.

Methods

In order to characterize the effects of oxidative stress on translation elongation we constructed a library of 61 plasmids, each coding for the green fluorescent protein (GFP) translationally fused to a different set of four identical codons.

Results

Using these reporters, we observed that …

Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov

Chemistry & Biochemistry Faculty Publications

n the present study, natural phaeosphaeride A (PPA) derivatives are synthesized. Anti-tumor studies are carried out on the PC3, K562, HCT-116, THP-1, MCF-7, A549, NCI-H929, Jurkat, and RPMI8226 tumor cell lines, and on the human embryonic kidney (HEK293) cell line. All the compounds synthesized turned out to have better efficacy than PPA towards the tumor cell lines listed. Among them, three compounds exhibited an ability to overcome the drug resistance of tumor cells associated with the overexpression of the P-glycoprotein by modulating the work of this transporter. Luminex xMAP technology was used to assess the effect of five synthesized compounds …

Escherichia Coli Alanyl-Trna Synthetase Maintains Proofreading Activity And Translational Accuracy Under Oxidative Stress, Arundhati Kavoor, Paul Kelly, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that synthesize aminoacyl-tRNAs to facilitate translation of the genetic code. Quality control by aaRS proofreading and other mechanisms maintains translational accuracy, which promotes cellular viability. Systematic disruption of proofreading, as recently demonstrated for alanyl-tRNA synthetase (AlaRS), leads to dysregulation of the proteome and reduced viability. Recent studies showed that environmental challenges such as exposure to reactive oxygen species can also alter aaRS synthetic and proofreading functions, prompting us to investigate if oxidation might positively or negatively affect AlaRS activity. We found that while oxidation leads to modification of several residues in Escherichia coli AlaRS, unlike …

Insights Into The Mechanisms Of Brain Endothelial Erythrophagocytosis, Jiahong Sun, Prema Vyas, Samar Mann, Annlia Paganini-Hill, Ane C. F. Nunes, Wei Ling Lau, David H. Cribbs, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

The endothelial cells which form the inner cellular lining of the vasculature can act as non-professional phagocytes to ingest and remove emboli and aged/injured red blood cells (RBCs) from circulation. We previously demonstrated an erythrophagocytic phenotype of the brain endothelium for oxidatively stressed RBCs with subsequent migration of iron-rich RBCs and RBC degradation products across the brain endothelium in vivo and in vitro, in the absence of brain endothelium disruption. However, the mechanisms contributing to brain endothelial erythrophagocytosis are not well defined, and herein we elucidate the cellular mechanisms underlying brain endothelial erythrophagocytosis. Murine brain microvascular endothelial cells (bEnd.3 …

Developmental Ethanol Exposure Causes Central Nervous System Dysfunction And May Slow The Aging Process In A Drosophila Model Of Fetal Alcohol Spectrum Disorder, Khaoula Belhorma, Nahed Darwish, Elizabeth Benn-Hirsch, Annalisa Duenas, Hillary Gates, Navneet Sanghera, Jodie Wu, Rachael L. French

Faculty Research, Scholarly, and Creative Activity

Alcohol is a known teratogen, and developmental exposure to ethanol results in fetal alcohol spectrum disorder (FASD). Children born with FASD can exhibit a range of symptoms including low birth weight, microcephaly, and neurobehavioral problems. Treatment of patients with FASD is estimated to cost 4 billion dollars per year in the United States alone, and 2 million dollars per affected individual's lifetime. We have established Drosophila melanogaster as a model organism for the study of FASD. Here we report that mutations in Dementin (Dmtn), the Drosophila ortholog of the Alzheimer's disease-associated protein TMCC2, convey sensitivity to developmental ethanol exposure, …

The Interconnectivity Of Parkinson's Disease And Type Two Diabetes Mellitus, Erica Olfson

Honors Scholars Collaborative Projects

This thesis is about the biochemical connection between Parkinson's disease and Type II Diabetes Mellitus.

Interplay Between Oxidative Stress, Sirt1, Reproductive And Metabolic Functions, Faiza Alam, Hareem Syed, Sofia Amjad, Mukhtiar Baig, Taseer Ahmed Khan, Rehana Rehman

Department of Biological & Biomedical Sciences

Silent information Regulators (SIRT1) gene stimulates antioxidants' expression, repairs cells damaged by oxidative stress (OS), and prevents the cells' dysfunction. In particular, the role of different Sirtuins, particularly SIRT1 in reproduction, has been widely studied over the past decade. Decreased SIRT 1 causes mitochondrial dysfunction by increasing Reactive Oxygen Species (ROS), lipid peroxidation, and DNA damage in both male and female gametes (Sperms and Oocytes), leading to infertility. In the female reproductive system, SIRT1 regulates proliferation and apoptosis in granulosa cells (GCs), and its down-regulation is associated with a reduced ovarian reserve. SIRT1 also modulates the stress response to OS …

Chronic Voluntary Alcohol Drinking Causes Anxiety-Like Behavior, Thiamine Deficiency, And Brain Damage Of Female Crossed High Alcohol Preferring Mice, Hong Xu, Hui Li, Dexiang Liu, Wen Wen, Mei Xu, Jacqueline A. Frank, Jing Chen, Haining Zhu, Nicholas J. Grahame, Jia Luo

Molecular and Cellular Biochemistry Faculty Publications

The central nervous system is vulnerable to chronic alcohol abuse, and alcohol dependence is a chronically relapsing disorder which causes a variety of physical and mental disorders. Appropriate animal models are important for investigating the underlying cellular and molecular mechanisms. The crossed High Alcohol Preferring mice prefer alcohol to water when given free access. In the present study, we used female cHAP mice as a model of chronic voluntary drinking to evaluate the effects of alcohol on neurobehavioral and neuropathological changes. The female cHAP mice had free-choice access to 10% ethanol and water, while control mice had access to water …

Aluminum Reproductive Toxicity: A Summary And Interpretation Of Scientific Reports, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Publications addressing aluminum (Al)-induced reproductive toxicity were reviewed. Key details were compiled in summary tables. Approximate systemic Al exposure, a measure of bioavailability, was calculated for each exposure, based on the Al percentage in the dosed Al species, Al bioavailability, and absorption time course reports for the exposure route. This was limited to laboratory animal studies because no controlled-exposure human studies were found. Intended Al exposure was compared to unintended dietary Al exposure. The considerable and variable Al content of laboratory animal diets creates uncertainty about reproductive function in the absence of Al. Aluminum-induced reproductive toxicity in female mice and …

Role Of Oxidative Stress And Altered Thyroid Hormones In Unexplained Infertility, Rehana Rehman, Hiba Ismail Rajpar, Mussarat Ashraf, Najeeha Talat Iqbal, Salima Lalani, Faiza Alam

Department of Biological & Biomedical Sciences

Objective: To explore the link between altered thyroid profile and oxidative stress marker in females with unexplained infertility.
Methods: The cross-sectional case-control study was carried out at the Islamabad Clinic Serving Infertile Couples, Islamabad, Pakistan, from June 2016 to August 2017, and comprised women aged 18-40 years regardless of ethnic background who were divided into two groups; those with unexplained infertility were the cases, while fertile women acted as the controls. Serum was analysed for triiodothyronine, thyroxine and thyroid stimulating hormone as well as for oxidative stress markers including manganese superoxide dismutase, glutathione reductase and adrenaline using enzymelinked immunosorbent assay. …

Deacetylation Of Hsd17b10 By Sirt3 Regulates Cell Growth And Cell Resistance Under Oxidative And Starvation Stresses., Lu Liu, Shuaiyi Chen, Miao Yu, Chenxu Ge, Mengmeng Ren, Boya Liu, Xin Yang, Thomas W Christian, Ya-Ming Hou, Junhua Zou, Wei-Guo Zhu, Jianyuan Luo

Department of Biochemistry and Molecular Biology Faculty Papers

17-beta-hydroxysteroid dehydrogenase 10 (HSD17B10) plays an important role in mitochondrial fatty acid metabolism and is also involved in mitochondrial tRNA maturation. HSD17B10 missense mutations cause HSD10 mitochondrial disease (HSD10MD). HSD17B10 with mutations identified from cases of HSD10MD show loss of function in dehydrogenase activity and mitochondrial tRNA maturation, resulting in mitochondrial dysfunction. It has also been implicated to play roles in the development of Alzheimer disease (AD) and tumorigenesis. Here, we found that HSD17B10 is a new substrate of NAD-dependent deacetylase Sirtuin 3 (SIRT3). HSD17B10 is acetylated at lysine residues K79, K99 and K105 by the acetyltransferase CBP, and the …

Repeatedly Heated Mix Vegetable Oils-Induced Atherosclerosis And Effects Of Murraya Koenigii, Gul Ambreen, Afshan Siddiq, Kashif Hussain, Abdul Saboor Hussain, Zara Naz

Department of Biological & Biomedical Sciences

Background: Statins are considered as standard drugs to control cholesterol levels, but their use is also associated with renal hypertrophy, hemorrhagic stroke, hepatomegaly, and myopathy. Murraya koenigii is an herb that is used in traditional cuisine and as a medicine in South Asia. Here we assessed the antidyslipidemic and antiatherosclerotic effects of this spice in repeated heated mix vegetable oils (RHMVO)-induced atherosclerotic models.
Methods: Aqueous extract of M. koenigii leaves (Mk LE) was prepared and its phytoconstituents were determined. Rabbits were divided into 5 groups (n = 10). Except for the control group, all the other four groups were treated …

Plant-Derived Natural Biomolecule Picein Attenuates Menadione Induced Oxidative Stress On Neuroblastoma Cell Mitochondria, Kavindra Kumar Kesari, Anupam Dhasmana, Shruti Shandilya, Neeraj Prabhakar, Ahmed Shaukat, Jinze Dou, Jessica M. Rosenholm, Tapani Vuorinen, Janne Ruokolainen

School of Medicine Publications and Presentations

Several bioactive compounds are in use for the treatment of neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. Historically, willow (salix sp.) bark has been an important source of salisylic acid and other natural compounds with anti-inflammatory, antipyretic and analgesic properties. Among these, picein isolated from hot water extract of willow bark, has been found to act as a natural secondary metabolite antioxidant. The aim of this study was to investigate the unrevealed pharmacological action of picein. In silico studies were utilized to direct the investigation towards the neuroprotection abilities of picein. Our in vitro studies demonstrate the neuroprotective properties …

Association Of Long-Term Consumption Of Repeatedly Heated Mix Vegetable Oils In Different Doses And Hepatic Toxicity Through Fat Accumulation, Gul Ambreen, Afshan Siddiq, Kashif Hussain

Department of Biological & Biomedical Sciences

Background: Hepatic diseases are one of the chief reasons for worldwide morbidity and mortality. The increased incidence in Asian countries is driving researchers to explore preventive ways from nature. It is more practical to go with healthy routine edibles like vegetable oils to avoid environmental and chemical hepatic injuries. With the use of thermally oxidized oils overproduction of reactive oxygen species (ROS) with overwhelmed cellular antioxidants defense system results in oxidative stress, the known cause of cardiovascular diseases (CVDs), cancers and neurodegenerative disorders. Little is investigated about the effect of daily used oxidized cooking oils on hepatic function changes with …

Quench Assisted (Quest) Mri Used As A Novel Approach To Identify Reactive Oxygen Species As A Result Of Experimental Tbi, Ethan M. Cohen, Eric Chang, Michael C. Schneider, Abigail Teitelbaum, Alexander R. Woznicki, Rachel E. Godfrey, Robert H. Podolsky, Karen L. Childers, Robin Roberts, Bruce A. Berkowitz, Kelly E. Bosse, Alana C. Conti

Medical Student Research Symposium

Introduction:

Traumatic brain injury (TBI) generates reactive oxygen species (ROS), promoting inflammatory processes and impeding TBI recovery. Within the VA population, over 70% of military personnel that sustain a TBI receive opioid-based pain relief, however, opiates may actually exacerbate post-TBI complications through its documented recruitment of oxidative and inflammatory systems. Thus, we hypothesize that TBI and opioid treatment act synergistically to worsen post-TBI oxidative stress.

Methods:

Mice were exposed to either TBI or sham injury and administered morphine or saline in the acute post-injury period. Afterwards, neuroimaging was conducted using a novel technique, QUEnch assiSTed (QUEST) MRI, which compares standard …

Evaluating The Anti-Cancer Efficacy Of A Synthetic Curcumin Analog On Human Melanoma Cells And Its Interaction With Standard Chemotherapeutics, Krishan Parashar, Siddhartha Sood, Ali Mehaidli, Colin Curran, Caleb Vegh, Christopher Nguyen, Christopher Pignanelli, Jianzhang Wu, Guang Liang, Yi Wang, Siyaram Pandey

Medical Student Research Symposium

Melanoma is the leading cause of skin-cancer related deaths in North America. Metastatic melanoma is difficult to treat and chemotherapies have limited success. Furthermore, chemotherapies lead to toxic side effects due to nonselective targeting of normal cells. Curcumin is a natural product of Curcuma longa (turmeric) and has been shown to possess anti-cancer activity. However, due to its poor bioavailability and stability, natural curcumin is not an effective cancer treatment. We tested synthetic analogs of curcumin that are more stable. One of these derivatives, Compound A, has shown significant anti-cancer efficacy in colon, leukemia, and triple-negative inflammatory breast cancer cells. …

Oxidative Stress And Male Infertility: A Cross Sectional Study, Rehana Rehman, Sofia Amjad, Hemaila Tariq, Nida Zahid, Masnoon Akhter, Mussarat Ashraf

Department of Biological & Biomedical Sciences

Objective: To compare stress markers and antioxidants in fertile and infertile males, and to explore their effects on reproductive hormones and fertility.
Methods: The cross-sectional case-control study was conducted from July 2017 to July 2018 at the Islamabad Clinic Serving Infertile Couples, Islamabad, Pakistan, and comprised male subjects aged 25-55 years. Infertile subjects were the cases, while healthy fertile males acted as the controls. Stress hormones cortisol and adrenaline and antioxidants glutathione peroxidase and superoxide dismutase were measured using enzyme-linked immunosorbent assay. Data was analysed using SPSS 22.
Results: Of the 376 subjects, 241(64%) were cases and 135(36%) were controls. …

Competing Reproductive And Physiological Investments In An All‑Female Lizard, The Colorado Checkered Whiptail, Lise M. Aubry, Spencer B. Hudson, Bryan M. Kluever, Alison C. Webb, Susannah S. French

USDA Wildlife Services: Staff Publications

Organisms in the wild have to allocate limited resources towards competing functions such as reproduction, growth, and self-maintenance. These competing investments create significant changes in physiological activity, and we still know little about the relationship between physiological activity and reproductive investment in natura. We investigated trade-offs between physiological activity and reproductive investment in the parthenogenetic Colorado checkered whiptail, Aspidoscelis neotesselata, across three different sites at the US Army Fort Carson Military Installation near Colorado Springs, CO, through-out the reproductive season in 2018 and 2019. We measured clutch size and reproductive activity and quantified plasma corticosterone (CORT), reactive oxygen metabolites (ROMs), …

Relationship Between Smoking Habit And Sperm Parameters Among Patients Attending An Infertility Clinic, Rehana Rehman, Nida Zahid, Sofia Amjad, Mukhtiar Baig, Zohair Jamil Gazzaz

Department of Biological & Biomedical Sciences

Background: This study aimed to estimate stress markers, oxidative stress (OS), reproductive hormones and sperm parameters in male smokers and non-smokers and observe the impact of oxidative stress markers and smoking on sperm count, motility and morphology in a selected population of Karachi, Pakistan.
Methods: This cross-sectional study was conducted from July 2017 to July 2018 at Aga Khan University (AKU), in Karachi, Pakistan. The subjects were recruited from the Sindh Institute of Reproductive Medicine (SIRM), Karachi based on defined inclusion criteria. The subjects were categorized into fertile and infertile based on cut off values of sperm parameters as recommended …

A Bird's-Eye View Of The Multiple Biochemical Mechanisms That Propel Pathology Of Alzheimer's Disease: Recent Advances And Mechanistic Perspectives On How To Halt The Disease Progression Targeting Multiple Pathways., Caleb Vegh, Kyle Stokes, Dennis Ma, Darcy Wear, Jerome Cohen, Sidhartha D. Ray, Siyaram Pandey

Touro College of Pharmacy (New York) Publications and Research

Neurons consume the highest amount of oxygen, depend on oxidative metabolism for energy, and survive for the lifetime of an individual. Therefore, neurons are vulnerable to death caused by oxidative-stress, accumulation of damaged and dysfunctional proteins and organelles. There is an exponential increase in the number of patients diagnosed with neurodegenerative diseases such as Alzheimer’s (AD) as the number of elderly increases exponentially. Development of AD pathology is a complex phenomenon characterized by neuronal death, accumulation of extracellular amyloid-β plaques and neurofibrillary tangles, and most importantly loss of memory and cognition. These pathologies are most likely caused by mechanisms including …

Microglia Are Both A Source And Target Of Extracellular Cyclophilin A, Gurkiran Kaur Flora, Ryan S. Anderton, Bruno P. Meloni, Gilles J. Guillemin, Neville W. Knuckey, Gabriella Macdougall, Vance Matthews, Sherif Boulos

Health Sciences Papers and Journal Articles

Glioblastoma (GBM) are lethal primary brain tumours whose pathogenesis is aided, at least partly, via a pro-tumorigenic microenvironment. This study investigated whether microglia, a cell component of the GBM microenvironment, mediates pro-tumorigenic properties via the action of cyclophilin A (CypA), a potent secretable chemokine and cytoprotectant that signals via the cell surface receptor, CD147. To this end, intracellular and secreted CypA expression was assessed in human primary microglia and BV2 microglial cells treated with the endotoxin, lipopolysaccharide (LPS) and the oxidative stress inducer, LY83583. We report that human primary microglia and BV2 microglia both express CypA and CD147, and that …

Intranasal Rapamycin Ameliorates Alzheimer-Like Cognitive Decline In A Mouse Model Of Down Syndrome, Antonella Tramutola, Chiara Lanzillotta, Eugenio Barone, Andrea Arena, Ilaria Zuliani, Luciana Mosca, Carla Blarzino, D. Allan Butterfield, Marzia Perluigi, Fabio Di Domenico

Chemistry Faculty Publications

Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression. Within this context, the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena. By our work we aimed to rescue mTOR signalling …

Iron-Dependent Cleavage Of Ribosomal Rna During Oxidative Stress In The Yeast Saccharomyces Cerevisiae, Jessica A Zinskie, Arnab Ghosh, Brandon M Trainor, Daniel Shedlovskiy, Dimitri G Pestov, Natalia Shcherbik

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Stress-induced strand breaks in rRNA have been observed in many organisms, but the mechanisms by which they originate are not well-understood. Here we show that a chemical rather than an enzymatic mechanism initiates rRNA cleavages during oxidative stress in yeast (Saccharomyces cerevisiae). We used cells lacking the mitochondrial glutaredoxin Grx5 to demonstrate that oxidant-induced cleavage formation in 25S rRNA correlates with intracellular iron levels. Sequestering free iron by chemical or genetic means decreased the extent of rRNA degradation and relieved the hypersensitivity of grx5Δ cells to the oxidants. Importantly, subjecting purified ribosomes to an in vitro iron/ascorbate …

Doxorubicin-Induced Elevated Oxidative Stress And Neurochemical Alterations In Brain And Cognitive Decline: Protection By Mesna And Insights Into Mechanisms Of Chemotherapy-Induced Cognitive Impairment ("Chemobrain"), Jeriel T. R. Keeney, Xiaojia Ren, Govind Warrier, Teresa Noel, David K. Powell, Jennifer M. Brelsfoard, Rukhsana Sultana, Kathryn E. Saatman, Daret K. St. Clair, D. Allan Butterfield

Chemistry Faculty Publications

Chemotherapy-induced cognitive impairment (CICI) is now widely recognized as a real and too common complication of cancer chemotherapy experienced by an ever-growing number of cancer survivors. Previously, we reported that doxorubicin (Dox), a prototypical reactive oxygen species (ROS)-producing anti-cancer drug, results in oxidation of plasma proteins, including apolipoprotein A-I (ApoA-I) leading to tumor necrosis factor-alpha (TNF-α)-mediated oxidative stress in plasma and brain. We also reported that co-administration of the antioxidant drug, 2-mercaptoethane sulfonate sodium (MESNA), prevents Dox-induced protein oxidation and subsequent TNF-α elevation in plasma. In this study, we measured oxidative stress in both brain and plasma of Dox-treated mice …

Extracellular Vesicles Released By Cardiomyocytes In A Doxorubicin-Induced Cardiac Injury Mouse Model Contain Protein Biomarkers Of Early Cardiac Injury, Chontida Yarana, Dustin W. Carroll, Jing Chen, Luksana Chaiswing, Yanming Zhao, Teresa Noel, Michael Alstott, Younsoo Bae, Emily V. Dressler, Jeffrey A. Moscow, D. Allan Butterfield, Haining Zhu, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Purpose—Cardiac injury is a major cause of death in cancer survivors, and biomarkers for it are detectable only after tissue injury has occurred. Extracellular vesicles (EV) remove toxic biomolecules from tissues and can be detected in the blood. Here, we evaluate the potential of using circulating EVs as early diagnostic markers for long-term cardiac injury.

Experimental Design—Using a mouse model of doxorubicin (DOX)-induced cardiac injury, we quantified serum EVs, analyzed proteomes, measured oxidized protein levels in serum EVs released after DOX treatment, and investigated the alteration of EV content.

Results—Treatment with DOX caused a significant increase in …

A Complex Molecular Switch Directs Stress-Induced Cyclin C Nuclear Release Through Scfgrr1-Mediated Degradation Of Med13., David C Stieg, Stephen D Willis, Vidyaramanan Ganesan, Kai Li Ong, Joseph Scuorzo, Mia Song, Julianne Grose, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

In response to oxidative stress, cells 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, which, with Med12 and Med13, associate with the core mediator complex of RNA polymerase II. In