Regulation of skeletal alpha actin expression during mu*

骨骼肌再生是一个基本的过程，它允许在一轮萎缩后恢复质量。 缺乏体力活动。不幸的是，在某些情况下，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应对机械负荷的增加。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 在骨骼肌在一轮萎缩后不能再生的情况下，这种机制是功能失调的。 肌肉质量的增加是在多个水平上调节的，包括转录、翻译和后调节。 翻译级。尽管，调节肌肉从一轮萎缩中恢复的关键分子机制 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，这一点尚不明确。 近年来，胰岛素样生长因子(IGF-I)被用于诱导骨骼肌肥大，挽救丢失的肌肉。 用于治疗肌营养不良症和肌萎缩侧索硬化症等神经肌肉疾病。 不幸的是，目前还不清楚IGF-I是如何对骨骼肌产生有益影响的。目前， 在肌肉再生过程中影响基因表达的转录机制还没有完全确定，而且 IGF-I与这些机制的潜在相互作用从未被探索过。对这一问题的理解 IGF-I激活的机制对肌肉生物学领域是至关重要的，因为它很难使用 人类医学中的IGF-I，由于IGF-I的许多不良副作用，包括癌症。一个潜在的方法是 避免副作用是为了了解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将描述独联体要素和 骨骼肌中骨骼肌α-肌动蛋白基因转录激活所需的转录因子 重生。不幸的是，到目前为止，还没有研究检查任何顺式元件和/或反式因子来调节 在骨骼肌萎缩的恢复期，任何基因的转录激活。特定目标2将 确定IGF-I通过特定顺式元件在骨骼α-肌动蛋白基因转录激活中的作用 以及骨骼肌再生过程中的转录因子。总体目标是确定IGF-I可能在 在肌肉再生过程中激活转录活性。

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.