RUNNING INDUCED INCREASE IN MUSCLE LPL MRNA

描述（改编自申请人摘要）：重要证据 提示骨骼肌脂蛋白脂酶（LPL）活性是 甘油三酯和脂蛋白代谢的决定因素。 公 证明运动训练增加骨骼肌LPL活性， 降低血浆甘油三酯，增加HDL-胆固醇，并降低 冠状动脉疾病的发病率。 的长期目标 建议的研究是确定，在LPL基因的水平上， 运动训练增加骨骼肌LPL mRNA的机制 表情 拟议研究的第一个目标是系统地 建立LPL mRNA表达的时间过程、运动持续时间和肌肉 在跑步训练的大鼠中增加。 据推测，在运动过程中， 训练后，LPL mRNA增加，每次运动后达到峰值， 然后逐渐福尔斯下降到未经训练的久坐水平 休息24-48小时。 还假设10分钟的 强烈的跑步或运动神经的电刺激就足够了 增加骨骼肌LPL mRNA。 这些研究将衡量 LPL在运动训练和安静时骨骼肌中转录率的变化 对照动物。 LPL启动子的缺失和突变实验将 确定运动诱导LPL的必需基因序列 启动子区。 计划进行替代实验，以测试 LPL的3 '-非翻译区参与引起 运动诱导的LPL表达增加。 这些发现将阐明 运动时LPL mRNA水平升高的分子机制 训练，因此将是必不可少的，以确定生化 参与运动的信号通路增加LPL表达， 改善血脂。 这些具体的目标是在连接的中间阶段 调节LPL表达的分子机制 冠状动脉疾病导致的发病率和死亡率， 死亡在美国。

DESCRIPTION (Adapted from the applicant's abstract): Significant evidence suggests that skeletal muscle lipoprotein lipase (LPL) activity is a major determinant of triglyceride and lipoprotein metabolism. It is well documented that exercise training increases skeletal muscle LPL activity, decreases plasma triglycerides, increases HDL-cholesterol, and reduces the incidence of coronary artery disease. The long-term objective of the proposed investigations is to determine, at the level of the LPL gene, the mechanisms(s) by which exercise training increases skeletal muscle LPL mRNA expression. The first aim of the proposed studies is to systematically establish the time course, exercise duration, and muscles that LPL mRNA is increased in run-trained rats. It is hypothesized that during exercise training, LPL mRNA increases after each exercise session to peak several hours after exercise and then gradually falls to untrained sedentary levels within 24-48 hours of rest. It is also hypothesized that 10 min. of intense running or electrical stimulation of the motor nerve is sufficient to increase skeletal muscle LPL mRNA. These studies will measure the transcription rate of LPL in skeletal muscles of run trained and sedentary control animals. Deletion and mutation experiments on the LPL promoter will determine essential and necessary gene sequences for exercise induced LPL promoter regions. Alternative experiments are planned to test for the involvement of the 3'-untranslated region of LPL in causing the exercise-induced increase in LPL expression. These findings will elucidate the molecular mechanism of increased LPL mRNA levels during exercise training, and thus will be essential for identifying the biochemical signaling pathway(s) involved in exercise increased LPL expression and improved blood lipids. These specific aims are at the interphase of linking molecular mechanisms regulating LPL expression to the prevention of morbidity and mortality caused by coronary artery disease, the leading cause of death in the United States.