AGING AND ADRENAL CATECHOLAMINE SYNTHESIS AND SECRETION

衰老与肾上腺儿茶酚胺的合成和分泌

• 批准号: 6371967
• 负责人: BRIAN A JACKSON
• 金额: $ 11.07万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6371967
• 关键词: RNase protection assay; adrenal medulla; aging; biological signal transduction; calcium channel; calcium flux; calcium ion; catecholamines; chromaffin cells; gene expression; immunocytochemistry; laboratory rat; messenger RNA; neurotransmitter agonist; neurotransmitter biosynthesis; nicotinic receptors; polymerase chain reaction; secretion; tissue /cell culture; tyrosine 3 monooxygenase; voltage gated channel; western blottings

A three-year career development plan is presented that will allow me to make a successful transition into conducting state-of the- art, extramurally funded aging research. With Dr. Phyllis M. Wise as my mentor, this plan will consist of a series of intensive training experiences with established investigators in the aging arena at the University of Kentucky. This training will allow me to develop a high level of expertise in electrophysiology (with Drs. McMahon and Landfield) and in molecular biology (with Drs. Wise and Estus), two areas in which I have relatively little experience, but which will be critical for both the successful completion of the studies proposed in this application as well as for the design and execution of future aging specific projects. In addition, I will receive training in confocal laser scanning microscopy with Dr. Mattson, which will dramatically enhance my current expertise in fluorescent imaging of intracellular Ca2+ dynamics. Experimentally, I will use chromaffin cells in short-term culture to test the hypothesis that the increased rate of adrenal medullary catecholamine secretion that occurs in aged subjects is the result of changes in nicotinic receptor-dependent increases in intracellular Ca2+ signaling via voltage-gated Ca2+ channels. The data derived from these studies will be incorporated into a comprehensive RO1 application that will be submitted toward the end of the training period. My long-term career objective is to maintain a vigorous, nationally and internationally respected research program in aging. This career development plan, coupled with the enormous wealth of aging-related research and academic resources that are available at the University of Kentucky, will allow me to achieve this objective.

提出了一项为期三年的职业发展计划，这将使我能够成功地过渡到进行最先进的，外部资助的衰老研究。 以Phyllis M. Wise博士为我的导师，该计划将包括一系列强化培训经验，与肯塔基大学老龄化竞技场的既定调查员进行了一系列密集的培训经验。 这项培训将使我能够在电生理学（McMahon博士和Landfield博士）和分子生物学（具有Wise和Estus博士）方面发展高水平的专业知识，这两个领域我的经验相对较少，但对于在此应用程序中的成功完成以及对未来特定特定特定特定特定的衰老项目的成功完成至关重要。此外，我将与Mattson博士接受共聚焦激光扫描显微镜的培训，这将显着增强我在细胞内CA2+动力学荧光成像方面的当前专业知识。在实验上，我将在短期培养中使用铬蛋白细胞来检验以下假设：在老年受试者中发生的肾上腺髓质儿茶酚胺分泌的速率增加是烟碱内CA2+信号通过电压芯孔的CA2+通道的细胞内CA2+信号传导中烟碱受体依赖性增加的结果。从这些研究中得出的数据将被纳入培训期结束时提交的全面RO1应用中。 我的长期职业目标是维持衰老方面的有力，在国内和国际尊重的研究计划。 这项职业发展计划，再加上肯塔基大学提供的大量与衰老有关的研究和学术资源，将使我能够实现这一目标。