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: 6167945
• 负责人: BRIAN A JACKSON
• 金额: $ 9.41万
• 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/6167945
• 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.

提出了一个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，额外资助的老龄化研究。 Phyllis M博士明智的作为我的导师，这个计划将包括一系列密集的培训经验，与既定的调查人员在老龄化竞技场在肯塔基州大学。 该培训将使我在电生理学（与McMahon博士和Landfield博士一起）和分子生物学（与Wise博士和Estus博士一起）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，但对于成功完成本申请中提出的研究以及未来老化特定项目的设计和执行至关重要。此外，我将接受Mattson博士的共聚焦激光扫描显微镜培训，这将大大提高我目前在细胞内Ca2+动态荧光成像方面的专业知识。实验上，我将使用短期培养的嗜铬细胞来检验这一假设，即老年受试者肾上腺髓质儿茶酚胺分泌速率的增加是烟碱受体依赖性细胞内Ca 2+信号通过电压门控Ca 2+通道增加的结果。从这些研究中获得的数据将被纳入一个全面的RO1申请，该申请将在培训期结束时提交。 我的长期职业目标是保持一个充满活力的，在国内和国际上受人尊敬的老龄化研究计划。 这个职业发展计划，再加上肯塔基州大学丰富的与衰老相关的研究和学术资源，将使我能够实现这一目标。