1,721,064 research outputs found
The effects of Akt overexpression in normal and dystrophic skeletal muscle
Full text linkLengthening (eccentric) contractions are known to induce skeletal muscle damage. Skeletal muscles of the dystrophin-deficient mdx mouse are especially sensitive to damage caused by lengthening contractions. Mild protocols of lengthening contractions, that cause no force decrement in normal mouse muscles, were found to cause a marked reduction in the maximal force produced by mdx muscles. The altered response of mdx muscles is considered to be due to sarcolemmal fragility, since no difference in force deficit after lengthening contractions was detected between mdx and control skinned fibers. We have developed an in vivo model to quantify the susceptibility of mdx mice muscles to eccentric contractions and showed a marked force decrease in the gastrocnemius of these animals.
We generated a transgenic mouse in which an inducible constitutively active form of Akt1 can be expressed selectively in adult skeletal muscle. We found that activation of Akt is sufficient to induce rapid and functional skeletal muscle hypertrophy. We crossed mdx mice with Akt transgenic mice and show a clear protection against damage from lengthening contractions after 3 weeks of Akt activation. Surprisingly, this protection is not correlated to muscle hypertrophy and is independent on the mTOR-pathway since rapamycin-treatment doesn’t inhibit the protective effect of Akt.
Protection against damage occurs on the mofibrillar level, most likely mitigated by an increase of utrophin leading to a reinforced cytoskeleton
Platelet-Derived Growth Factor signaling and the role of cellular crosstalk in functional muscle growth
No full text
Effect of loading and unloading on skeletal muscle
No full textIt is well established that the amount of loading placed on a muscle significantly alters its size and
composition. If loading placed on a muscle is reduced, for example during longterm bed rest or
during low gravity conditions, muscle mass will decrease and its fibre type composition changes
leading to significant functional limitations. On the other hand, increasing the mechanical load leads
to increases in muscle size, as, for example, can clearly be seen in bodybuilders. How a muscle
‘feels’ the mechanical loading placed upon it, and how it translates this mechanical signal into the
phenotypical adaptations is still poorly understood.
In this chapter we will discuss in detail the models which are available to study various muscle
loading conditions, i.e. muscle unloading, muscle overloading, extreme muscle loading which leads
to muscle damage, and how these conditions eventually change the phenotype observed. We discuss
in detail the various intra- and extramuscular sensors which respond to changes in loading
conditions. The extramuscular proprioceptive system is briefly discussed and an up to date review is
given on the possible intracellular sensors present. Finally, some important signaling pathways
involved in leading to the changes in gene transcription are summarized briefly.
This chapter therefore gives an overview of the current state of knowledge and of the questions still
open regarding the mechanical sensing-and signal transduction in skeletal muscle and the models
which can be used to study this intriguing phenomena
The functional significance of the skeletal muscle clock: Lessons from Bmal1 knockout models
Full text linkThe circadian oscillations of muscle genes are controlled either directly by the intrinsic muscle clock or by extrinsic factors, such as feeding, hormonal signals, or neural influences, which are in turn regulated by the central pacemaker, the suprachiasmatic nucleus of the hypothalamus. A unique feature of circadian rhythms in skeletal muscle is motor neuron-dependent contractile activity, which can affect the oscillation of a number of muscle genes independently of the muscle clock. The role of the intrinsic muscle clock has been investigated using different Bmal1 knockout (KO) models. A comparative analysis of these models reveals that the dramatic muscle wasting and premature aging caused by global conventional KO are not present in muscle-specific Bmal1 KO or in global Bmal1 KO induced in the adult, therefore must reflect the loss of Bmal1 function during development in non-muscle tissues. On the other hand, muscle-specific Bmal1 knockout causes impaired muscle glucose uptake and metabolism, supporting a major role of the muscle clock in anticipating the sleep-to-wake transition, when glucose becomes the predominant fuel for the skeletal muscle
Protocol for measuring force in skinned diaphragm muscle fibers of myopathic SEPN1 knockout mice following chronic tauroursodeoxycholic acid treatment
Full text link: Selenoprotein N1 (SEPN1) is a type II endoplasmic reticulum (ER) glycoprotein. Loss-of-function mutations in the gene encoding for SEPN1 give rise to myopathy. Here, we present a protocol for evaluating the contractility of diaphragmatic muscle fibers of SEPN1 knockout mice following chronic treatment with tauroursodeoxycholic acid (TUDCA). We describe steps for genotyping SEPN1 knockout mice, TUDCA in vivo treatment, diaphragm dissection, and chemical permeabilization. We then detail procedures for single muscle fiber isolation and tension measurement. For complete details on the use and execution of this protocol, please refer to Germani et al.1
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