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Cellular and Molecular Physiology Commons™
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Articles 1 - 15 of 15
Full-Text Articles in Cellular and Molecular Physiology
Exposure To Pm2.5 And Aging., Daniel Chris Gomes
Exposure To Pm2.5 And Aging., Daniel Chris Gomes
Electronic Theses and Dissertations
Inhalation of fine airborne particulate matter (PM2.5) is an environmental risk factor for numerous health disorders, including cardiovascular diseases (CVD). While several studies have shown that PM2.5 exposure can induce oxidative stress, DNA damage, and inflammation, the underlying mechanisms that translate these effects into systemic pathology remain poorly understood. Some recent studies have shown that PM2.5 exposure can lead to telomere shortening in leukocytes, but the generality of this outcome and contribution to endothelial dysfunction has not yet been fully explored. We hypothesized that PM2.5inhalation accelerates cellular aging and senescence in both circulating peripheral …
Metabolic Regulation Of Cardiac Fibroblast Phenotype And Function., Collin Kleis Wells
Metabolic Regulation Of Cardiac Fibroblast Phenotype And Function., Collin Kleis Wells
Electronic Theses and Dissertations
Cardiac fibroblasts are central effectors of cardiac repair after myocardial infarction (MI). In response to signaling cues, they differentiate to a range of phenotypes with robust capacities to synthesize and secrete extracellular matrix (ECM) and signaling molecules. Although activated fibroblast phenotypes are associated with pronounced changes in metabolism, it remains unclear how the metabolic network upholds the effector functions of fibroblasts in the post-infarcted heart. Here, we identified that critical enzymes in the phosphoenolpyruvate (PEP) cycle, i.e. pyruvate kinase muscle-2 (PKM2) and phosphoenolpyruvate carboxykinase-2 (PCK2), are elevated in the heart after MI and examined their role in regulating post-MI remodeling …
Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson
Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson
Electronic Theses and Dissertations
Microvascular disease is hallmarked by pathophysiological conditions such as endothelial senescence, intimal thickening which impairs vasodilation, and regression of the capillary beds causing tissue ischemia in the myocardium or in peripheral vascular networks. Adipose-derived stromal vascular fraction (SVF) has previously demonstrated the ability to revascularize tissue. Increasing evidence shows that regenerative cells elicit their therapeutic benefit by paracrine mechanisms, leaving open extracellular vesicles (EVs) as a potential crux of the cell therapy paradigm. To test this idea, three types of gelatin methacrylate hydrogels were employed: SVF gels, EV gels derived from SVF, and blank control gels, which were used in-vitro …
Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller
Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller
Electronic Theses and Dissertations
28% of drug withdrawal from the market are due to unforeseen disruptions in cardiomyocyte contractility and electrophysiology. The most commonly used platforms for drug testing are in vivo animal models and in vitro cell culture models. While both have been of paramount importance for the discovery and detection of many cardiotoxicities and mechanisms of action, they lack the ability to model an intact human myocardium. This work aims to establish cardiac tissue slices, which are 300-micron thin tissue sections taken from the left ventricular myocardium, as an alternative platform for cardio-oncology studies, specifically cardiotoxicity testing. Additionally, this work aims to …
Pyridine Nucleotide Redox Potential In Coronary Smooth Muscle Couples Myocardial Blood Flow To Cardiac Metabolism., Marc Matthew Dwenger
Pyridine Nucleotide Redox Potential In Coronary Smooth Muscle Couples Myocardial Blood Flow To Cardiac Metabolism., Marc Matthew Dwenger
Electronic Theses and Dissertations
The maintenance of myocardial oxygen supply during stress is essential for sustaining cardiac health. Enhancement of coronary blood flow upon increases in myocardial oxygen demand (i.e., hyperemia) relies on regulation of voltage-gated K+ (Kv) channels by their intracellular β subunits (i.e., Kvβ proteins). Considering that, Kvβ proteins are aldo-keto reductases (AKRs) and regulate Kv channel gating, we tested the hypothesis that elevation of myocardial oxygen demand modifies intracellular NAD(H) in arterial myocytes. Furthermore, we tested whether the resultant change in the redox state of the pyridine nucleotide pool directly regulates coronary Kv1 channel activity. High-resolution imaging mass spectrometry and …
The Identification Of Long Non-Coding Rna Zfas1 Through An Exploratory Rna-Sequencing Analysis And Its Association With Epithelial-To-Mesenchymal Transition In Colon Cancer Adenocarcinoma., Stephen J. O'Brien
Electronic Theses and Dissertations
Colorectal adenocarcinoma is the fourth most common cancer diagnosed worldwide and is a significant cause of morbidity and mortality. This dissertation performed an exploratory RNA-sequencing analysis comparing gene expression between colon adenocarcinoma tissue and paired normal colon epithelium. After identification of a number of lncRNAs that were increased in expression in colon adenocarcinoma compared to normal colon epithelium, we aimed to validate the expression and investigate their function in vitro. Specifically, we focused on the lncRNA ZFAS1 and its association with epithelial-to-mesenchymal transition. These studies found the following: 1. Seven candidate lncRNAs were identified from the exploratory RNA-sequencing analysis to …
Mitochondrial Transcription Factor A'S Role In Heart Failure., George H. Kunkel
Mitochondrial Transcription Factor A'S Role In Heart Failure., George H. Kunkel
Electronic Theses and Dissertations
Background: An essential mitochondrial component, Mitochondrial Transcription Factor A (TFAM) is reduced within the failing heart. TFAM maintains regulatory functions of cardiomyocyte physiology and stability. Mitochondrial Transcription Factor A forms a mitochondrial nucleoid anti-oxidant structure and reduces pathophysiological abnormalities to structural and contractile proteins. Overall, this functions to physically stabilize mtDNA. Significant molecular changes such as a loss of TFAM drive pathophysiological concentrations of cytoplasmic Ca2+ and reactive oxygen species. Both of these factors induce proteolytic enzymes to degrade the physiological cardiomyocyte. In TFAMs absence, heart function deteriorates and hypertrophic expansion ensues: thereby changing the physiological myocardium to a pathological …
Enhancing Cell Therapy For Ischemic Cardiomyopathy., Michael J. Book
Enhancing Cell Therapy For Ischemic Cardiomyopathy., Michael J. Book
Electronic Theses and Dissertations
Cardiac cell therapy using cardiac mesenchymal cells (CMC) significantly reduces ventricular dysfunction in patients with ischemic cardiomyopathy. Despite the improvement in function, a modest number of CMCs survive in the heart post-transplantation. In this study, we sought to improve the survival and retention of transplanted CMCs to prolong the therapeutic benefits afforded by cardiac cell therapy. To do this, we targeted the enzyme telomerase (TERT), known to be active in some highly proliferating cells (e.g. germ, stem). TERT is responsible for preventing telomere attrition, thereby allowing continued proliferation. TERT has also been shown to be protective, improve cell migration and …
Cardiovascular And Hematopoietic Responses To Volatile Benzene Exposure., Wesley Tyler Abplanalp
Cardiovascular And Hematopoietic Responses To Volatile Benzene Exposure., Wesley Tyler Abplanalp
Electronic Theses and Dissertations
The rapid and recent increase in the global epidemic of diabetes and cardiovascular disease suggests a strong component of the environment is contributing. Benzene is a ubiquitous volatile pollutant generated by cigarette smoke, automobile exhaust, wildfires and industrial activities. Consequently, it is found in almost all urban and rural air samples. Benzene is known to cause hematotoxicity and its metabolism generates oxidative stress. Although, benzene has been studied for many years, few investigations have probed what influence benzene exposure may have on other physiological processes. Here we hypothesize that benzene metabolism by hepatic-CYP450 2E1 generates oxidative stress and inflammation, which …
Cryopreservation Of Hepatocyte (Hepg2) Cell Monolayers: Impact Of Trehalose, Blake Stokich, Quinn Osgood, David Grimm, Shhyam Moorthy, Nilay Chakraborty, Michael Menze
Cryopreservation Of Hepatocyte (Hepg2) Cell Monolayers: Impact Of Trehalose, Blake Stokich, Quinn Osgood, David Grimm, Shhyam Moorthy, Nilay Chakraborty, Michael Menze
Faculty and Staff Scholarship
A simple method to cryogenically preserve hepatocyte monolayers is currently not available but such a technique would facilitate numerous applications in the field of biomedical engineering, cell line development, and drug screening. We investigated the effect of trehalose and dimethyl sulfoxide (Me2SO) in cryopreservation of human hepatocellular carcinoma (HepG2) cells in suspension and monolayer formats. HepG2 cell monolayers were incubated for 24 h at varying concentrations of trehalose (50–150 mM) prior to cryopreservation to identify the optimum concentration for such preincubation. When trehalose alone was used as the cryoprotective agent (CPA), cells in monolayer format did not survive freezing while …
Improved Tolerance To Salt And Water Stress In Drosophila Melanogaster Cells Conferred By Late Embryogenesis Abundant Protein., Matthew Marunde, Dilini Samarajeewa, John Anderson, Shumin Li, Steven Hand, Michael Menze
Improved Tolerance To Salt And Water Stress In Drosophila Melanogaster Cells Conferred By Late Embryogenesis Abundant Protein., Matthew Marunde, Dilini Samarajeewa, John Anderson, Shumin Li, Steven Hand, Michael Menze
Faculty and Staff Scholarship
Mechanisms that govern anhydrobiosis involve the accumulation of highly hydrophilic macromolecules, such as late embryogenesis abundant (LEA) proteins. Group 1 LEA proteins comprised of 181 (AfLEA1.1) and 197 (AfLEA1.3) amino acids were cloned from embryos of Artemia franciscana and expressed in Drosophila melanogaster cells (Kc167). Confocal microscopy revealed a construct composed of green fluorescence protein (GFP) and AfLEA1.3 accumulates in the mitochondria (AfLEA1.3-GFP), while AfLEA1.1-GFP was found in the cytoplasm. In the presence of mixed substrates, oxygen consumption was statistically identical for permeabilized Kc167 control and Kc167-AfLEA1.3 cells. Acute titrations of permeabilized cells with NaCl up to 500 mM led …
Diapause And Anhydrobiosis In Embryos Of Artemia Franciscana : Metabolic Depression, Lea Proteins And Water Stress., Steven Handel, Yuvraj Patil, Shumin Li, Nilay Charkraborty, Arpurva Borcar, Michael Menze, Leaf Boswell, Daniel Moore, Mehmet Toner
Diapause And Anhydrobiosis In Embryos Of Artemia Franciscana : Metabolic Depression, Lea Proteins And Water Stress., Steven Handel, Yuvraj Patil, Shumin Li, Nilay Charkraborty, Arpurva Borcar, Michael Menze, Leaf Boswell, Daniel Moore, Mehmet Toner
Faculty and Staff Scholarship
Metabolic depression is typically correlated with extended survival of environmental challenge and energy-limitation in early life stages of various invertebrates and vertebrates. Diapause is an ontogenetically-programmed reduction of development and often metabolism seen in many invertebrates. When embryos of Artemia franciscana enter the state of diapause, the overall metabolic depression is estimated to be greater than 99%. These embryos also contain trehalose and express multiple isoforms of Late Embryogenesis Abundant (LEA) proteins, constituents often present in a number of such anhydrobiotic animals. The mRNA levels for LEA proteins are highest in diapause and post-diapause embryos that possess desiccation tolerance, but …
Late Embryogenesis Abundant Proteins Protect Human Hepatoma Cells During Acute Desiccation., Shumin Li, Nilay Chakraborty, Apurva Borcar, Michael Menze, Mehmet Toner, Steven Hand
Late Embryogenesis Abundant Proteins Protect Human Hepatoma Cells During Acute Desiccation., Shumin Li, Nilay Chakraborty, Apurva Borcar, Michael Menze, Mehmet Toner, Steven Hand
Faculty and Staff Scholarship
Expression of late embryogenesis abundant (LEA) proteins is highly correlated with desiccation tolerance in anhydrobiotic animals, selected land plants, and bacteria. Genes encoding two LEA proteins, one localized to the cytoplasm/nucleus (AfrLEA2) and one targeted to mitochondria (AfrLEA3m), were stably transfected into human HepG2 cells. A trehalose transporterwas used for intracellular loading of this disaccharide. Cellswere rapidly and uniformly desiccated to low water content (< 0.12 g H2O/g dry weight) with a recently developed spin-drying technique. Immediately on rehydration, control cells without LEA proteins or trehalose exhibited 0% membrane integrity, comparedwith 98% in cells loaded with trehalose and expressing AfrLEA2 or AfrLEA3m; surprisingly, AfrLEA3m without trehalose conferred 94% protection. Cell proliferation across 7 d showed an 18-fold increase for cells dried with AfrLEA3m and trehalose, compared with 27-fold for nondried controls. LEA proteins dramatically enhance desiccation tolerance in mammalian cells and offer the opportunity for engineering biostability in the dried state.
Metabolic Preconditioning Of Mammalian Cells : Mimetic Agents For Hypoxia Lack Fidelity In Promoting Phosphorylation Of Pyruvate Dehydrogenase., Apurva Borcar, Michael Menze, Mehmet Toner, Steven Hand
Metabolic Preconditioning Of Mammalian Cells : Mimetic Agents For Hypoxia Lack Fidelity In Promoting Phosphorylation Of Pyruvate Dehydrogenase., Apurva Borcar, Michael Menze, Mehmet Toner, Steven Hand
Faculty and Staff Scholarship
Induction of HIF-1α by oxygen limitation promotes increased phosphorylation and catalytic depression of mitochondrial pyruvate dehydrogenase (PDH) and an enhanced glycolytic poise in cells. Cobalt chloride and desferrioxamine are widely used as mimics for hypoxia because they increase the levels of HIF-1α. We evaluated the ability of these agents to elicit selected physiological responses to hypoxia as a means to metabolically precondition mammalian cells, but without the detrimental effects of hypoxia. We show that, while CoCl2 does increase HIF-1α in a dose-dependent manner, it unexpectedly and strikingly decreases PDH phosphorylation at E1α sites 1, 2, and 3 (Ser293, Ser300, and …
Long-Term Survival Of Anoxia Despite Rapid Atp Decline In Embryos Of The Annual Killifish Austrofundulus Limnaeus., Jason Podrabsky, Michael Menze, Steven Hand
Long-Term Survival Of Anoxia Despite Rapid Atp Decline In Embryos Of The Annual Killifish Austrofundulus Limnaeus., Jason Podrabsky, Michael Menze, Steven Hand
Faculty and Staff Scholarship
Embryos of the annual killifish Austrofundulus limnaeus can survive for months in the complete absence of oxygen. Survival of anoxia is associated with entry into a state of metabolic dormancy known as diapause. However, extreme tolerance of anoxia is retained for several days of post-diapause development. Rates of heat dissipation in diapause II and 4 days post-diapause II embryos were measured under aerobic conditions and during the transition into anoxia. Phosphorylated adenylate compounds were quantified in embryos during entry into anoxia and after 12 hr of aerobic recovery. Rates of heat dissipation were not affected by exposure to anoxia in …