Regulation of skeletal alpha actin expression during mu*

mu* 期间骨骼 α 肌动蛋白表达的调节

• 批准号: 7198071
• 负责人: ESPEN E SPANGENBURG
• 金额: $ 7.21万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7198071
• 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

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过程，可以在由肌肉引起的萎缩后恢复质量。 身体不活动。不幸的是，在某些情况下，例如衰老、高血压或糖尿病，骨骼 肌肉不会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，并确定是否 当骨骼肌在一次萎缩后无法再生时，这些机制就会出现功能障碍。 肌肉质量的增加受到多个层面的调节，包括转录、翻译和后处理。 翻译水平。尽管如此，调节肌肉从萎缩中恢复的关键分子机制 虽然尚未明确，但众所周知，内源性生长因子在刺激肌肉生长中发挥着不可或缺的作用。 最近，胰岛素样生长因子（IGF-I）已被用于诱导骨骼肌肥大，以挽救失去的肌肉 老年动物的肿块并治疗神经肌肉疾病，如肌营养不良症和肌萎缩侧索硬化症。 不幸的是，目前尚不清楚 IGF-I 如何对骨骼肌产生有益作用。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，并且进一步 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至关重要，因为它很难使用 IGF-I 在人类医学中的应用，是由于 IGF-I 有许多不良副作用，包括癌症。一种潜在的方法 规避副作用的方法是了解 IGF-I 改变骨骼肌的细胞机制，然后 通过药理学手段调节这些机制。具体目标 1 将描述顺式元素和 骨骼肌过程中骨骼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，迄今为止，还没有研究检查任何调节顺式元件和/或反式因子 骨骼肌萎缩恢复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肌动蛋白基因转录激活的作用 和骨骼肌再生过程中的转录因子。总体目标是确定 IGF-I 在 在肌肉再生过程中激活转录活性。