The ARCC is a professional event organized by graduate students and postdoctoral fellows from Ohio University, West Virginia University, Marshal University and the University of Kentucky. The event was designed to facilitate professional networking and resource sharing among graduate students and postdoctoral fellows in the field of cell biology in the Appalachian region, while highlighting the area as a rapidly emerging center of student-driven research. This year the event took place on Saturday, Oct. 26, at the West Virginia University Robert C. Byrd Health Sciences Center in Charleston, WV, attracting 93 total registrants and included 40 registered poster presentations.
In the Cancer 2 category,
1st Place: Yanrong Qian, “Extracellular ATP mediated intracellular ATP increase: Evidence for transport of extracellular ATP into cancer cells” Yanrong Qian; Yi Liu; Yunsheng Li; Xuan Wang; Robert Colvin; Xiaozhuo Chen (Ohio University)
Abstract: ATP as a most common cofactor of enzymatic reactions and a universal source of bioenergy transfer plays central roles in both normal and cancer cells. Almost all cancer cells switch from the highly efficient mitochondrial oxidative phosphorylation to low efficiency glycolysis for ATP synthesis, a phenomenon called the Warburg effect that remains to be fully understood. Despite the low efficiency glycolysis, cancer cells appear to have no shortage of ATP under any circumstance examined. In fact, ample evidence indicates intratumoral (extracellular) ATP concentration is higher than other parts of the body. However, it is presently unclear about the sources and fates of intratumoral/extracellular ATP and how they affect intracellular ATP. We previously reported drastic increases of intracellular ATP concentration and rescue of glucose deprived A549 human lung cancer cells by addition of extracellular ATP. We hypothesized that the increased intracellular ATP is a result of extracellular ATP taken up by cancer cells. To test this hypothesis, we studied extracellular ATP-induced intracellular ATP increase in A549 lung and other cancer and non-tumorigenic cells using the ATP assay. Here we report that extracellular ATP increased intracellular ATP of A549 cells in dose- and time-dependent manners, even when cells’ ATP synthesis were blocked. The ATP increase was absent in the non-tumorigenic cell lines under the same conditions. Furthermore, extracellular ATP led to changes in energy status sensing protein AMPK and its phosphorylation. All these results indicate that extracellular ATP exerts profound effects on intracellular ATP and suggest a possible direct ATP transport mechanism into cancer cells. These results strongly suggest that cancer cells supplement their ATP need with extracellular ATP and extracellular ATP may play some vitally important but previously unrecognized roles in the Warburg effect and tumorigenesis. These new findings also imply a new strategy for cancer treatment.
In the Combined Category 2 (Developmental Biology, Neuroscience)
Runner-up: Amrita Basu, “Quantitative Analysis of Gene Expression in the Brain of Transgenic bGH and Wild Type Mice” Amrita Basu; John J. Kopchick (Ohio University)
Abstract: The presence of growth hormone (GH) and GH receptor (GHR) in various regions of the mammalian brain as observed in experimental and/or physiological alteration of GH signaling [e.g. acromegaly (increased GH action), dwarfism (reduced GH action) and Laron Syndrome (disrupted GH signaling due to non-functional GHR)], indicate possible involvement of GH in development and function of the central nervous system, e.g. neuronal proliferation, cognition, memory and aging. Comprehensive understanding of GH function in the brain, as a diabetogenic hormone (due to anti-insulin action) and primary regulator of insulin like growth factor-1 (IGF-1) production, will help in elucidating role of GH in normal brain and in Alzheimer’s disease (AD), a neurodegenerative disease associated with perturbed glucose metabolism and insulin/IGF-1 signaling in the brain. The present study aimed at quantitative estimation of eight genes (GH, GHR, IGF-1, IGF-1 receptor, insulin, insulin receptor, monoamine oxidase (MAO) A and B) in six months old, male, transgenic giant bovine growth hormone (bGH) mice (model of acromegaly) compared to wild type littermates. Following total RNA isolation, cDNA synthesis, quantitative real time polymerase chain reaction (qPCR) and data analysis, up-regulated expression of GH and IGF-1 and down-regulation of GHR, IGF-1 receptor, insulin, insulin receptor, MAO-A and MAO-B mRNA transcript abundance were observed in various brain regions in bGH mice, relative to controls. Further proteomic analysis of the brain tissue of these animals will be performed for a better understanding of the molecular effect of GH in the brain and to identify potential therapeutic targets in GH signaling pathway, relevant to AD and other neuronal diseases. This work was supported in part by the State of Ohio’s Eminent Scholar Program that includes a gift from Milton and Lawrence Gall, by the AMVETS, by the Diabetes Research Initiative at Ohio University, and by NIH grants DK083729, AG031736.
In the Combined Category 3 (Diabetes, Immunology)
1st Place: Adam Jara, “Disruption of cardiac growth hormone receptor (GHR) in adult mice alters fat mass and systemic glucose homeostasis” Adam Jara; Xingbo Liu, Chance Benner, Don Sim, Edward O List, Darlene E Berryman, John J Kopchick (Ohio University)
Abstract: GH is a central mediator of metabolism and is necessary for the proper development and maintenance of several tissues, including the heart. To better understand the effects that GH action has on cardiac tissue, we have recently developed a tamoxifen-inducible, cardiac-specific GHR disrupted (iC-GHRKO) mouse. Four-month-old iC-GHRKO mice (n=8) were injected with tamoxifen (80mg/kg) and subjected to echocardiography evaluation (8 and 12 months) and insulin and glucose tolerance testing (6 and 12 months). Beginning two weeks after tamoxifen injection, and repeated monthly, fasting glucose, body composition, and blood pressure measurements were performed. iC-GHRKO mice showed no difference in basal cardiac function at both 8 and 12 months of age nor did they demonstrate any difference in longitudinal systolic blood pressure. Surprisingly, iC-GHRKO mice were significantly more insulin sensitive at 6 months of age and had less fat mass versus controls. By 12 months of age iC-GHRKO mice were significantly less glucose tolerant and less insulin sensitive. Subsequent immunoblot analysis of insulin signaling in heart and quadricep muscle demonstrated that iC-GHRKO mice had decreased insulin stimulated Akt phosphorylation in heart and decreased insulin stimulated MAPK phosphorylation in quadricep muscle. These data indicate that altered cardiac GH signaling may influence whole body metabolism. Future work will focus on identifying the nature of the altered insulin signaling and exploring the presence of paracrine factors from the heart (cardiokines) which may influence peripheral tissues.