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Regulation of skeletal alpha actin expression during mu*

mu* 期间骨骼 α 肌动蛋白表达的调节

基本信息

批准号：
7434515
负责人：
ESPEN E SPANGENBURG
金额：
$ 7.07万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-09 至 2009-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7434515
关键词：
Actins Acute Address Adverse effects Age Amphibia Amyotrophic Lateral Sclerosis Animals Area Atrophic Award Bed rest Biochemical Biology Cloning Complementary DNA Condition Congestive Heart Failure Contractile Proteins Coupling Data Development Diabetes Mellitus Elements Endocrine Environment Event Funding Future Gene Activation Gene Expression Gene Transfer Genes Goals Grant Growth Growth Factor Human Hypertension Immunohistochemistry In Situ In Vitro Individual Injury Insulin-Like Growth Factor I Intention Laboratories Laboratory Research Lead Malignant Neoplasms Measurement Measures Mechanics Medicine Membrane Mind Missouri Molecular Muscle Muscle Fatigue Muscle Fibers Muscle function Muscular Atrophy Muscular Dystrophies Myoblasts NIH Program Announcements Neuromuscular Diseases Personal Satisfaction Physiological Physiology Play Postdoctoral Fellow Preparation Primary Cell Cultures Principal Investigator Process Production Protein Isoforms Proteins Purpose Rattus Recovery Recovery of Function Regulation Research Research Personnel Reverse Transcriptase Polymerase Chain Reaction Role Running Sarcoplasmic Reticulum Scientist Skeletal Muscle Skeletal system Skin Somatomedins Space Flight Students Support of Research Techniques Thinking Time Training Transcriptional Activation Transfection Universities Viral Western Blotting aged alpha Actin autocrine career middle age muscle hypertrophy paracrine post-doctoral training programs protein expression satellite cell skeletal muscle plasticity skills stem transcription factor vector

项目摘要

Skeletal muscle regrowth is a fundamental process that allows the recovery of mass after a bout of atrophy induced by physical inactivity. Unfortunately, under some circumstances, such as aging, hypertension, or diabetes, the skeletal muscle does not respond to increases in mechanical load by increasing muscle mass. The long term objective is to determine the cellular/molecular mechanisms that regulate muscle regrowth under healthy conditions, and determine if the mechanisms are dysfunctional in conditions where skeletal muscle does not regrow after a bout of atrophy. Increases in muscle mass are regulated at multiple levels, including the transcriptional, translational, and post- translational level. Although, key molecular mechanisms that regulate the recovery of muscle from a bout of atrophy remain undefined, it is well known that endogenous growth factors play an integral role in stimulating muscle growth. Recently, insulin-like growth factor (IGF-I) has been used to induce skeletal muscle hypertrophy, to rescue lost muscle mass in aged animals and to treat neuromuscular diseases such as muscular dystrophy and amyotrophic lateral sclerosis. Unfortunately, it is unclear how IGF-I is impacting beneficial effects on the skeletal muscle. Currently, the transcriptional mechanisms that impact gene expression during muscle regrowth are not completely defined, and further the potential interaction of IGF-I with these mechanisms has never been explored. The understanding of the mechanisms activated by IGF-I is of fundamental importance to the muscle biology field, since it will be difficult to use IGF-I in human medicine, due to the numerous undesired side effects of IGF-I, including cancer. One potential way to circumvent the side effects is to understand the cellular mechanisms by which IGF-I alters skeletal muscle, and then modulate these mechanisms through pharmacological means. Specific Aim 1will delineate the cis elements and the transcription factors necessary for transcriptional activation of the skeletal a-actin gene during skeletal muscle regrowth. Unfortunately to date, no studies have examined any cis-elements and/or trans-factors that regulate transcriptional activation of any gene during recovery from a bout of skeletal muscle atrophy. Specific Aim 2 will determine the role IGF-I, has on the transcriptional activation of the skeletal a-actin gene through specific cis-elements and transcription factors during skeletal muscle regrowth. The overall goal is to determine the role IGF-I may have in activating transcriptional activity during muscle regrowth.

骨骼肌再生是一个基本的过程，允许恢复后的一轮萎缩引起的质量身体不活动。不幸的是，在某些情况下，如衰老、高血压或糖尿病，肌肉不通过增加肌肉质量来响应机械负荷的增加。长期目标是确定在健康条件下调节肌肉再生的细胞/分子机制，在骨骼肌在一次萎缩后不能再生的情况下，这些机制是功能失调的。肌肉质量的增加在多个水平上受到调节，包括转录、翻译和后表达。翻译水平。虽然，调节肌肉从萎缩中恢复的关键分子机制尽管尚未明确，但众所周知，内源性生长因子在刺激肌肉生长方面发挥着不可或缺的作用。近年来，胰岛素样生长因子（IGF-I）被用于诱导骨骼肌肥大，以挽救失去的肌肉用于治疗老年动物的肌肉萎缩症和肌萎缩性侧索硬化症等神经肌肉疾病。不幸的是，目前还不清楚IGF-I如何影响骨骼肌的有益作用。目前在肌肉再生过程中影响基因表达的转录机制尚未完全确定， IGF-I与这些机制的潜在相互作用从未被探索过。的理解 IGF-I激活的机制对于肌肉生物学领域具有根本的重要性，因为它将难以使用由于IGF-I的许多不良副作用，包括癌症，IGF-I在人类医学中的应用。一种可能的方法是规避副作用的方法是了解IGF-I改变骨骼肌的细胞机制，通过药理学手段调节这些机制。具体目标1将描述顺式元件和骨骼肌生长过程中骨骼肌α-肌动蛋白基因转录激活所必需的转录因子再生不幸的是，到目前为止，还没有研究检查任何顺式元件和/或反式因子，在从骨骼肌萎缩中恢复的过程中，任何基因的转录激活。具体目标2将确定IGF-I通过特定顺式元件对骨骼α-肌动蛋白基因转录激活的作用和转录因子。总的目标是确定IGF-I可能在在肌肉再生过程中激活转录活性。