Physiology Commons^™

A Critical Role For Staphylococcal Nitric Oxide Synthase In Controlling Flavohemoglobin Toxicity, Ryan M. Singh, Sujata S. Chaudhari, Sasmita Panda, Elizabeth H. Hutfless, Cortney E. Heim, Dhananjay Shinde, Abdulelah A. Alqarzaee, Margaret F. Sladek, Vineet Kumar, Matthew C. Zimmerman, Paul D. Fey, Tammy Kielian, Vinai Chittezham Thomas

Journal Articles: Cellular & Integrative Physiology

Most coagulase-negative staphylococcal species, including the opportunistic pathogen Staphylococcus epidermidis, struggle to maintain redox homeostasis and grow under nitrosative stress. Under these conditions, growth can only resume once nitric oxide (NO) is detoxified by the flavohemoglobin Hmp. Paradoxically, S. epidermidis produces endogenous NO through its genetically encoded nitric oxide synthase (seNOS) and heavily relies on its activity for growth. In this study, we investigate the basis of the growth advantage attributed to seNOS activity. Our findings reveal that seNOS supports growth by countering Hmp toxicity. S. epidermidis relies on Hmp activity for its survival in the host under NO stress. …

Mechanistic Insight Into Chronic Stress-Induced Cerebrovascular Dysfunction, Emily Nicole Burrage

Graduate Theses, Dissertations, and Problem Reports

Despite decades of research psychological stress remains a prevalent problem in society, often diminishing quality of life and increasing the risk of developing dementia. The brain plays a central role in the response to stress and as it is unable to store energy substrates, the brain relies heavily on dynamically regulated blood flow. Therefore, it is important that there is a tight coupling between neural activity and cerebral blood flow to meet metabolic demands and maintain critical brain function. It has been established that chronic psychological stress has detrimental effects on cerebrovascular function, potentially through increased superoxide anion production through …

Characterizing The Effects Of Pyrroloquinoline Quinone (Pqq) Supplementation On Skeletal Muscle Mitochondrial Function And Myogenesis During Oxidative Stress And Iugr., Allyson J. Wood

Electronic Thesis and Dissertation Repository

Intrauterine growth restriction (IUGR) affects 10-15% of births and is associated with placental insufficiency (PI), resulting in fetal oxidative stress (OS). This OS is a factor in the predisposition to postnatal noncommunicable disease (NCD) of which muscle mitochondrial dysfunctional is a key aspect. Pyrroloquinoline quinone (PQQ), an antioxidant-like compound, is capable of OS reduction and promotes mitochondrial function, though limited research has focused on its effects in in utero skeletal muscle. This study sought to investigate the impact of in vitro H₂O₂, a model of OS, and an in vivo model of OS associated IUGR, with …

The Impact Of Age/Rage Signaling On Oxidative Stress Under Diabetic Conditions In Cardiac Fibroblasts, Christopher Dorroh

Honors Theses

Diabetes is a major health concern in the United States, with 1.5 million new cases diagnosed each year. Patients who suffer from diabetes have an increased risk of developing heart failure, a form of cardiovascular disease. Heart failure has been shown to result from increased left ventricular stiffness, which in turn is caused by increased remodeling of the extracellular matrix (ECM). This increase in ECM remodeling is a result of AGE/RAGE signaling, which occurs at a heightened level in the cardiac fibroblast cells of diabetics. Studies have shown that diabetics have elevated levels of AGEs (Advanced Glycation End-Products), which bind …

Dysregulation Of Daf-16/Foxo3a-Mediated Stress Responses Accelerates T Oxidative Dna Damage Induced Aging, Aditi U. Gurkar, Andria R. Robinson, Yuxiang Cui, Xuesen Li, Shailaja K. Allani, Amanda Webster, Mariya Muravia, Mohammad Fallahi, Herbert Weissbach, Paul D. Robbins, Yinsheng Wang, Eric E. Kelley, Claudette M. St. Croix, Laura J. Niedernhofer, Matthew S. Gill

Faculty & Staff Scholarship

DNA damage is presumed to be one type of stochastic macromolecular damage that contributes to aging, yet little is known about the precise mechanism by which DNA damage drives aging. Here, we attempt to address this gap in knowledge using DNA repair-deficient C. elegans and mice. ERCC1-XPF is a nuclear endonuclease required for genomic stability and loss of ERCC1 in humans and mice accelerates the incidence of age-related pathologies. Like mice, ercc-1 worms are UV sensitive, shorter lived, display premature functional decline and they accumulate spontaneous oxidative DNA lesions (cyclopurines) more rapidly than wild-type worms. We found that ercc-1 worms …

The Role Of Oxidative Stress In The Establishment Of Resistance To Cisplatin In Epithelial Ovarian Cancer Cells, Jimmy Belotte

Wayne State University Dissertations

Epithelial ovarian cancer is the deadliest of all gynecologic cancers with an estimated 22,280 new cases and 14,240 deaths expected in 2016 in the US alone. This high mortality rate can be partially attributed to a lack of universal screening and the development of resistance to the recommended chemotherapeutics. Typically, the treatment of ovarian cancer requires both cytoreductive surgery (CRS) and platinum/taxane combination chemotherapy. Initially, 50–80% of patients with advanced disease will achieve complete clinical response. Unfortunately, most will relapse within 18 months with chemoresistant disease. Thus, understanding the mechanisms of platinum resistance is critical in order to improve the …

The Role Of Oxidative Stress In The Mechanisms Of Ammonia-Induced Brain Swelling And Tolerance In The Goldfish (Carassius Auratus), David F. Jones Lisser Mr.

Theses and Dissertations (Comprehensive)

Toxic build-ups of ammonia can cause potentially fatal brain swelling in mammals, but such swelling is reversible in the anoxia- and ammonia-tolerant goldfish (Carassius auratus). The mechanisms of ammonia-induced brain swelling and tolerance remain elusive, but several studies have suggested a role for reactive oxygen species (ROS), which may damage proteins and lipids in the plasma membrane of astrocytes in the brain. As a result, osmotic gradients across cell membranes may be altered leading to water uptake by astrocytes and swelling. While a role for ROS has been proposed in mammals, no studies have addressed this question in …

Effects Of The Developmental Environment On Oxidative Damage And Antioxidants In Red-Eared Slider Turtle ( Trachemys Scripta Elegans ) Hatchlings, Lisa Allison Treidel

Theses and Dissertations

Developmental environments influence many individual phenotypes. However, currently we have a limited understanding of how the developmental environment influences oxidative stress resistance phenotypes. Oxidative stress is defined as a physiological state during which the production of harmful free radicals exceeds the protective capabilities of antioxidants. Variations among adults in susceptibility to oxidative stress can have important consequences for life history strategies and fitness related traits. Our work was aimed at providing insight in to the role that the developmental environment plays on oxidative stress phenotypes in the model oviparous reptile the red-eared slider turtle (Trachemys scripta elegans). Here, we conducted …

Exercise In Individuals With Down Syndrome: A Brief Review, Rachel L. Kerstiens, Matt Green

International Journal of Exercise Science

International Journal of Exercise Science 8(2): 192-201, 2015. Research examining acute and long-term responses to exercise of individuals with Downs Syndrome (DS) is sparse. However, if this group experiences benefits associated with improved quantity or quality of life, it would be important to elucidate specific responses and discourage adoption of a sedentary lifestyle in individuals with DS. Specifically, these individuals have multiple blunted physiological responses to exercise both at the onset and termination of an acute exercise bout. Mechanistically, this could be rooted in hormonal responses which are blunted, in comparison to non-DS participants. Specific studies indicate individuals with …

Functional Importance Of Oxidative Post-Translational Modifications Of Ryanodine Receptor In Cardiac Sarcoplasmic Reticulum Ca2+ Handling During Oxidative Stress, Stefan R. Mazurek

Dissertations

Free ionic calcium (Ca2+) plays an essential role as a second messenger that initiates muscle contraction in the heart. Ryanodine receptor (RyR2) acts as the primary Sarcoplasmic Reticulum (SR) Ca2+ release channel in the heart. In the event that intracellular SR Ca2+ handling is compromised, both the contractility and electrical excitability of the heart can be altered. As a consequence, heart function may not be able to maintain the necessary cardiac output to meet the metabolic demand of the body.

Increased oxidation of RyR2 has been implicated in abnormal Ca2+ handling that promotes the onset and progression of cardiovascular disease. …

Med13p Prevents Stress-Independent Mitochondrial Hyperfragmentation And Aberrant Apoptosis Activation In Saccharomyces Cerevisiae By Controlling Cyclin C Nuclear Localization, Svetlana Khakhina

Graduate School of Biomedical Sciences Theses and Dissertations

During aging, and as a result of environmental changes, cells are exposed to elevated levels of reactive oxygen species (ROS). High ROS levels induce lipid oxidation, protein aggregation, mitochondrial hyperfragmentation, DNA damage and programmed cell death (PCD), also called apoptosis. PCD is a highly regulated process and its misregulation has been linked to neurodegenerative diseases and cancer development.

Our hypothesis is that cyclin C plays a role in the initiation of apoptosis. During normal conditions, cyclin C represses the transcription of stress response genes (SRG). In response to stress, cyclin C translocates to the cytoplasm where it facilitates mitochondrial hyperfragmentation …

The Role Of Oxidative Stress In The Pathogenesis Of Epithelial Ovarian Cancer, Nicole Marie King

Wayne State University Dissertations

Ovarian cancer is the leading cause of death from gynecologic malignancies yet the underlying pathophysiology is not clearly established. The disease is usually diagnosed in the advanced stage and carries a poor prognosis. The 5-year survival rate is greater than 75% if diagnosis of the cancer occurs at an early stage; however, this rate drops to 20% when the tumor has spread beyond its origin. Thus, a method for early detection is critically needed, which can help prolong, or even save lives. Currently, an effective screening test for ovarian cancer is lacking. Many tests have been evaluated but have been …