Physiology Commons^™

Maintenance Of Mitochondrial Genomic Integrity In The Absence Of Manganese Superoxide Dismutase In Mouse Liver Hepatocytes., Anthony R. Cyr, Kyle E. Brown, Michael L. Mccormick, Mitchell C. Coleman, Adam J. Case, George S. Watts, Bernard W. Futscher, Douglas R. Spitz, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

Manganese superoxide dismutase, encoded by the Sod2 gene, is a ubiquitously expressed mitochondrial antioxidant enzyme that is essential for mammalian life. Mice born with constitutive genetic knockout of Sod2 do not survive the neonatal stage, which renders the longitudinal study of the biochemical and metabolic effects of Sod2 loss difficult. However, multiple studies have demonstrated that tissue-specific knockout of Sod2 in murine liver yields no observable gross pathology or injury to the mouse. We hypothesized that Sod2 loss may have sub-pathologic effects on liver biology, including the acquisition of reactive oxygen species-mediated mitochondrial DNA mutations. To evaluate this, we established …

Loss Of Dendritic Inhibition In The Hippocampus After Repeated Early-Life Hyperthermic Seizures In Rats., Richard Boyce, L Stan Leung

Physiology and Pharmacology Publications

Seizures are relatively common in children and are a risk factor for subsequent temporal lobe epilepsy. To investigate whether early-life seizures themselves are detrimental to the proper function of the adult brain, we studied whether dendritic excitation and inhibition in the hippocampus of adult rats were altered after hyperthermia-induced seizures in immature rats. In particular, we hypothesized that apical dendritic inhibition in hippocampal CA1 pyramidal cells would be disrupted following hyperthermia-induced seizures in early life. Seizure rats were given three hyperthermia-induced seizures per day for three days from postnatal day (PND) 13 to 15; control rats were handled similarly but …

Androgen Receptor-Target Genes In African American Prostate Cancer Disparities, Bi-Dar Wang, Qi Yang, Kristin Ceniccola, Fernando Bianco, Ramez Andrawis, Thomas W. Jarrett, Harold A. Frazier, Steven R. Patierno, Norman H. Lee

Pharmacology and Physiology Faculty Publications

The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an integrative approach combining gene expression profiling and pathway and promoter analyses to investigate differential transcriptomes and deregulated signaling pathways in AA versus CA cancers. A comparison of AA and CA PCa specimens identified 1,188 differentially expressed genes. Interestingly, these transcriptional differences were overrepresented in signaling pathways that converged on the androgen receptor (AR), suggesting that the AR may be a unifying oncogenic theme in AA PCa. Gene promoter …

Aging And Sympathetic Neurotransmission In Two Strains Of Rats That Differ In Longevity And Immune Profiles, Sam David Perez

Loma Linda University Electronic Theses, Dissertations & Projects

Age-related changes in sympathetic neurotransmission in immune organs may be associated with immunosenescence; however no causal relationship has been established. From previous studies in Fischer rats (F344), we have found that during middle age, sympathetic nerve activity (SNA) rises in the spleen followed by a decline in noradrenergic (NA) innervation. Also, increased sympathetic signaling via betaadrenergic receptor (β-AR) and reduced proliferation of lymphocytes are evident with increasing age. Although SNA progressively rises with age, effects of age on sympathetic factors may be different across rat strains. If causal relationships exist between sympathetic activity and immune function, they may be related …

Aberrant Promoter Cpg Methylation Is A Mechanism For Impaired Phd3 Expression In A Diverse Set Of Malignant Cells., Trenton L. Place, Matthew P. Fitzgerald, Sujatha Venkataraman, Sabine U. Vorrink, Adam J. Case, Melissa L.T. Teoh, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: The prolyl-hydroxylase domain family of enzymes (PHD1-3) plays an important role in the cellular response to hypoxia by negatively regulating HIF-α proteins. Disruption of this process can lead to up-regulation of factors that promote tumorigenesis. We observed decreased basal expression of PHD3 in prostate cancer tissue and tumor cell lines representing diverse tissues of origin. Furthermore, some cancer lines displayed a failure of PHD3 mRNA induction when introduced to a hypoxic environment. This study explores the mechanism by which malignancies neither basally express PHD3 nor induce PHD3 under hypoxic conditions.

METHODOLOGY/PRINCIPAL FINDINGS: Using bisulfite sequencing and methylated DNA enrichment …

Human Chondrosarcoma Cells Acquire An Epithelial-Like Gene Expression Pattern Via An Epigenetic Switch: Evidence For Mesenchymal-Epithelial Transition During Sarcomagenesis., Matthew P. Fitzgerald, Francoise Gourronc, Melissa L.T. Teoh, Matthew J. Provenzano, Adam J. Case, James A. Martin, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

Chondrocytes are mesenchymally derived cells that reportedly acquire some epithelial characteristics; however, whether this is a progression through a mesenchymal to epithelial transition (MET) during chondrosarcoma development is still a matter of investigation. We observed that chondrosarcoma cells acquired the expression of four epithelial markers, E-cadherin,desmocollin 3, maspin, and 14-3-3σ, all of which are governed epigenetically through cytosine methylation. Indeed, loss of cytosine methylation was tightly associated with acquired expression of both maspin and 14-3-3σ in chondrosarcomas. In contrast, chondrocyte cells were negative for maspin and 14-3-3σ and displayed nearly complete DNA methylation. Robust activation of these genes was also …

Interaction Between Adrenergic And Nitric Oxide-Releasing Nerves In Cerebral Arteries, Emmanuel Ngu Mbaku

Loma Linda University Electronic Theses, Dissertations & Projects

Of all body tissues, the brain is the least tolerant of ischemia so much that interruption of cerebral blood flow by 5 sec can cause syncope, with irreversible tissue damage if the ischemia last a few minutes. In this respect, the body has an imperative duty of ensuring constant and adequate blood supply to the brain. It does so through a series of intrinsic and extrinsic control factors of which adrenergic and nitric oxide-releasing nerves are components. My research examined the interaction between these two nerve-types with emphasis on the mechanisms involved as well as on changes in their functions …

Chronic Hypoxia, Exercise Training, And Skeletal Muscle Capillarity: Angiogenic Regulation And Morphological Consequences, Ivan Mark Olfert

Loma Linda University Electronic Theses, Dissertations & Projects

Angiogenesis is important in health and disease. In particular, exercise training is known to increase skeletal muscle capillarity, providing there is sufficient training intensity. The stimulus for this may be intracellular hypoxia activating angiogenic growth factor gene expression. Acute hypoxia alone has been shown to increase the gene expression of several key angiogenic regulators, e.g. vascular endothelial growth factor (VEGF) and to a lesser degree transforming growth factor-β1 (TGF-β1), basic fibroblast growth factor (bFGF), and thrombospondin-1 (TSP-1), an endogenous negative angiogenic regulator. Paradoxically, however, chronic hypoxia is generally not found to increase mammalian skeletal muscle capillarity. Accordingly, we hypothesized that …

Pathological Physiology As A Basis For Medical Practice, Walter E. Macpherson

Medical Arts and Sciences: A Scientific Journal of the College of Medical Evangelists

No abstract provided.