Systems and Integrative Physiology Commons^™

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 E. Podrabsky, Michael A. Menze, Steven C. Hand

Faculty Research & Creative Activity

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 …

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 …

Regulation Of Endothelial Nitric Oxide Synthase In Pulmonary Myofibroblasts, Jonathan David Faughn

Masters Theses & Specialist Projects

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease leading to decreased lung volume and eventual respiratory failure. At present, the median post-diagnosis lifespan is between three and six years. Myofibroblasts are collagen-secreting cells essential for wound healing, but also implicated in the fibroproliferation and extra cellular matrix deposition commonly seen in IPF. The nitric oxide (NO) signaling pathway is implicated in protomyofibroblast to myofibroblast transition and regulation. Previous work has shown that in pulmonary myofibroblasts, endothelial nitric oxide synthase (eNOS) is the primary NOS isoform expressed. The current study used cultured rat pulmonary myofibroblasts between passages two and five …

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 …

Poisonous Rangeland Plants In San Luis Obispo County, Sara Litten, Amanda Ou

Animal Science

Poisonous Rangeland Plants in San Luis Obispo County is a comprehensive educational guide to rangeland plants that are toxic to domestic livestock. This guide begins with an exploration of how the biological systems are affected by the poisonous plant toxins. The biochemistry behind these toxins is included in the discussion. Next, reference material for fourteen plants that inhabit San Luis Obispo County is provided. This information includes specific toxins found in poisonous plants, affected animals, symptoms of poisoning, stages of growth, lethal dose, and distribution of the plant in California. This section of the guide is filled with helpful photos …