OXIDATIVE STRESS INDUCED APOPTOSIS IN CARDIAC MYOCYTES

描述 (摘自申请者摘要)申请者的长期职业目标是 在基础水平上有助于我们对分子的理解 心力衰竭的机制。他的短期职业目标是：1) 深入了解和学习可用于测量和 生命系统中活性氧物种(ROS)的控制；2)用途 用于操作和测量的各种分子生物学技术 在培养的心肌细胞中的转录事件；3)然后在体内使用 心肌损伤的动物模型和验证假说的转基因动物 在文化体系中发展起来的。这位候选人于1990年获得博士学位。 利用单通道电生理学研究脂蛋白相互作用， 在布里格姆妇女医院度过了过去的5年 内科和心脏病学方面的临床培训。在那里，他开始 研究ROS介导的心肌损伤的机制，特别是， 程序性细胞死亡。他最近搬到波士顿医疗中心去了 继续这些努力。心脏病学和医学的特殊兴趣 Ros的教职员工为他提供了一个肥沃的环境来发展他的 科学的想法。他将测试的假设是，特别是ROS 超氧阴离子和/或羟基自由基，可引发细胞凋亡 以及心肌细胞能够调节它们的 细胞毒转录调控对这些物种的易感性 防御系统。首先，他将使用培养的成年和新生大鼠 以准确检测哪些ROS可诱导心肌细胞凋亡 培养的心肌细胞。其次，他将研究预适应 刺激可以增加特定的细胞毒性防御系统的活性，并在 这一途径可防止ROS介导的心肌细胞凋亡。第三， 使用腺病毒转导系统，他将研究 超氧化物歧化酶或过氧化氢酶的过度表达可以预防 ROS诱导心肌细胞凋亡。最后，他将审查是否 过表达锰依赖超氧化物歧化酶的转基因小鼠 增加了心肌梗死后心肌细胞凋亡的易感性 脑梗塞。

DESCRIPTION (Adapted from applicants' abstract) The applicant's long term career goal is to contribute at a basic level to our understanding of the molecular mechanisms of heart failure. His short term career objectives are: 1) to gain insight into and learn techniques available for the measurement and manipulation of reactive oxygen species (ROS) in living systems; 2) use various molecular biological techniques for the manipulation and measurement of transcriptional events in cultured myocytes; 3) and then use in vivo animal models of myocardial injury and transgenic animals to test hypotheses developed in culture systems. The candidate received his Ph.D. in 1990 studying lipid protein interactions using single channel electrophysiology, and has spent the last 5 years at Brigham and Women's Hospital completing my clinical training in internal medicine and cardiology. There he began to study the mechanisms of ROS mediated myocardial injury, specifically, programmed cell death. He recently moved to Boston Medical Center to continue these efforts. The particular interest of cardiology and medicine faculty there in ROS provides a fertile environment for him to develop his scientific ideas. The hypotheses he will test are that ROS, in particular superoxide anion and/or hydroxyl radicals, can trigger apoptosis in ventricular myocytes, and that myocytes are able to regulate their susceptibility to these species by transcriptional regulation of cytotoxic defense systems. Firstly, he will use cultured adult and neonatal rat ventricular myocytes to examine exactly which ROS can induce apoptosis in cultured myocytes. Secondly, he will examine whether preconditioning stimuli can increase activities of specific cytotoxic defense systems and in this way prevent ROS-mediated apoptosis in ventricular myocytes. Thirdly, using an adenovirus transfection system, he will study whether over-expression of superoxide dismutase or catalase can protect against ROS-Induced apoptosis in cardiac myocytes. Finally, he will examine whether transgenic mice over-expressing manganese-dependent superoxide dismutase have increased susceptibility to myocardial apoptosis after myocardial infarction.