DEFECTIVE ALPHA, ADRENERGIC SIGNALING IN SENESCENT RAT

衰老大鼠的α、肾上腺素信号传导缺陷

• 批准号: 6221353
• 负责人: DONNA HOPE KORZICK
• 金额: $ 4.22万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 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 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6221353
• 关键词: age difference; aging; alpha adrenergic receptor; animal old age; biological signal transduction; diacylglycerols; exercise; heart; heart contraction; heart function; immunocytochemistry; inositol phosphates; laboratory rat; messenger RNA; northern blottings; protein isoforms; protein kinase C; receptor coupling; receptor sensitivity; second messengers

Donna H. Korzick, Ph.D. is a physiologist currently supported by a T32 Training National Research Service Award from NIH. Dr. Korzick has demonstrated significant commitment to research activities in the area of adrenergic regulation of cardiac contractile function as it pertains to chronic endurance exercise and cardiac pathophysiology. The KO1 Mentored Research Scientist Development Award would enable her to build upon past research experiences and compliment her current research skills with the intent of establishing an independent reseach career in the field of cardiovascular aging. Career Development/Training Plan: The training activities outlined for the duration of this award include a particular emphasis on acquisition of a significant number of molecular and biochemical techniques in the area of receptor-second messenger coupling. Attendance of seminars in pharmacology, physiology and veterinary biomedical sciences will foster interactions with individuals with diverse backgrounds and interests. A unique aspect of this plan includes the team of consulting mentors associated with this application. A team of renowned investigators are committed to Dr. Korzick's mentoring and training with regard to their respective disciplines and direct interactions will occur as needed. Research Plan: An important compensatory role for the alpha1-adrenergic receptor (alpha1-AR) system in regulating cardiac contractile function in a variety of cardiac pathologies has recently been proposed. Observations from senescent myocardium, however, suggest the inotropic responsiveness of the heart to alpha1-AR stimulation is blunted rather than enhanced, further diminishing the functional reserve capacity of the aging rat ventricle. Preliminary studies suggest that this response may be mediated by diminished effectiveness of the PKC-dependent arm of the alpha1-AR signal transduction pathway. The contribution of other alpha1-AR signaling cascade components are unknown. This proposal will systematically evaluate cellular changes in alpha1-AR signal transduction responsible for alpha1-AR contractile dysfunction in rat heart. Studies will also address the role of chronic exercise in attenuating age-related aberrations in alpha1-AR mediated contractile function and underlying mechanisms. Environment: The environment surrounding Dr. Korzick at the University of Missouri is one marked by a commitment to research and academic scholarship with major strengths in cardiovascular sciences.

唐娜·H Korzick博士是一位生理学家，目前获得NIH的T32培训国家研究服务奖。 Korzick博士已经证明了对心脏收缩功能肾上腺素能调节领域研究活动的重大承诺，因为它涉及慢性耐力运动和心脏病理生理学。 KO 1指导研究科学家发展奖将使她能够建立在过去的研究经验和恭维她目前的研究技能，建立在心血管衰老领域的独立研究事业的意图。 职业发展/培训计划：培训活动概述了该奖项的持续时间包括特别强调在受体-第二信使耦合领域获得大量的分子和生物化学技术。 参加药理学，生理学和兽医生物医学科学的研讨会将促进与不同背景和兴趣的个人的互动。 该计划的一个独特方面包括与此应用程序相关的咨询顾问团队。 一个由著名研究人员组成的团队致力于Korzick博士在各自学科方面的指导和培训，并将根据需要进行直接互动。研究计划：最近提出了α 1-肾上腺素能受体（α 1-AR）系统在多种心脏病理中调节心脏收缩功能的重要代偿作用。然而，对衰老心肌的观察表明，心脏对α 1-AR刺激的变力性反应是钝化的而不是增强的，进一步降低了衰老大鼠心室的功能储备能力。 初步研究表明，这种反应可能是由α 1-AR信号转导通路的PKC依赖性臂的有效性降低介导的。 其他α 1-AR信号级联组件的贡献是未知的。 本研究将系统评价大鼠心脏α 1-AR收缩功能障碍中α 1-AR信号转导的细胞变化。 研究还将探讨长期运动在减弱α 1-AR介导的收缩功能中与年龄相关的畸变中的作用及其潜在机制。工作环境：密苏里州大学的Korzick博士周围的环境是以致力于心血管科学的研究和学术奖学金为标志的。