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·科齐克博士是一位生理学家，目前获得 NIH T32 培训国家研究服务奖的支持。 Korzick 博士致力于心脏收缩功能的肾上腺素能调节领域的研究活动，因为它涉及慢性耐力运动和心脏病理生理学。 KO1 指导研究科学家发展奖将使她能够在过去的研究经验的基础上，补充她目前的研究技能，以期在心血管衰老领域建立独立的研究生涯。 职业发展/培训计划：该奖项期间概述的培训活动包括特别强调获得受体-第二信使偶联领域的大量分子和生化技术。 参加药理学、生理学和兽医生物医学科学研讨会将促进与具有不同背景和兴趣的个人的互动。 该计划的一个独特之处包括与该应用程序相关的咨询导师团队。 由著名研究人员组成的团队致力于对 Korzick 博士进行各自学科的指导和培训，并根据需要进行直接互动。研究计划：最近提出了α1-肾上腺素能受体（α1-AR）系统在调节多种心脏病中的心脏收缩功能中的重要代偿作用。然而，对衰老心肌的观察表明，心脏对α1-AR刺激的正性肌力反应减弱而不是增强，进一步削弱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 α1-AR 信号转导途径中 PKC 依赖性臂的有效性降低介导的。 其他 α1-AR 信号级联成分的贡献尚不清楚。 该提案将系统地评估导致大鼠心脏 α1-AR 收缩功能障碍的 α1-AR 信号转导的细胞变化。 研究还将探讨长期运动在减轻 α1-AR 介导的收缩功能和潜在机制中与年龄相关的畸变中的作用。环境： 密苏里大学 Korzick 博士周围的环境致力于研究和学术学术，在心血管科学方面具有主要优势。