Changes in PKB/Akt and calcineurin signaling during recovery in atrophied soleus muscle induced by unloading

Sugiura, T.; Abe, Noritaka; Nagano, Masahide; Goto, Katsumasa; Sakuma, Kunihiro; Naito, Hisashi; Yoshioka, Toshitada; Powers, Scott K.

doi:10.1152/ajpregu.00688.2004

Cited by 65 publications

(74 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although Akt phosphorylation appeared to be attenuated after HS, this effect did not reach statistical significance in either muscle. This may be attributed to the low baseline levels of Akt phosphorylation in both muscles, because previous studies showed that skeletal muscle unloading or inactivity is accompanied by decreased Akt phosphorylation (29,53). Subsequently, consequent to decreased Akt activity, reduced mRNA translation (2, 10) and increased protein degradation resulting from decreased suppression of atrogin expression (46) likely contributed to the loss of muscle mass.…”

Section: Discussionmentioning

confidence: 99%

Myogenic differentiation during regrowth of atrophied skeletal muscle is associated with inactivation of GSK-3β

Velden

Langen²,

Kelders³

et al. 2007

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Myogenic differentiation during regrowth of atrophied skeletal muscle is associated with inactivation of GSK-3β

Velden

Langen²,

Kelders³

et al. 2007

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…Many of the classic anabolic and catabolic pathways are affected in response to denervation and inactivity. Myostatin expression is increased (94) and activation of Akt is decreased (104) in inactive skeletal muscle. Recently, some novel mechanisms have been implicated in denervation and unloading-induced atrophy.…”

Section: Tgf-␤mentioning

confidence: 98%

The ubiquitin proteasome system in atrophying skeletal muscle: roles and regulation

Bilodeau

Coyne

Wing

2016

American Journal of Physiology-Cell Physiology

128

View full text Add to dashboard Cite

Bilodeau PA, Coyne ES, Wing SS. The ubiquitin proteasome system in atrophying skeletal muscle: roles and regulation. Am J Physiol Cell Physiol 311: C392-C403, 2016. First published August 10, 2016; doi:10.1152/ajpcell.00125.2016.-Muscle atrophy complicates many diseases as well as aging, and its presence predicts both decreased quality of life and survival. Much work has been conducted to define the molecular mechanisms involved in maintaining protein homeostasis in muscle. To date, the ubiquitin proteasome system (UPS) has been shown to play an important role in mediating muscle wasting. In this review, we have collated the enzymes in the UPS whose roles in muscle wasting have been confirmed through loss-of-function studies. We have integrated information on their mechanisms of action to create a model of how they work together to produce muscle atrophy. These enzymes are involved in promoting myofibrillar disassembly and degradation, activation of autophagy, inhibition of myogenesis as well as in modulating the signaling pathways that control these processes. Many anabolic and catabolic signaling pathways are involved in regulating these UPS genes, but none appear to coordinately regulate a large number of these genes. A number of catabolic signaling pathways appear to instead function by inhibition of the insulin/IGF-I/protein kinase B anabolic pathway. This pathway is a critical determinant of muscle mass, since it can suppress key ubiquitin ligases and autophagy, activate protein synthesis, and promote myogenesis through its downstream mediators such as forkhead box O, mammalian target of rapamycin, and GSK3␤, respectively. Although much progress has been made, a more complete inventory of the UPS genes involved in mediating muscle atrophy, their mechanisms of action, and their regulation will be useful for identifying novel therapeutic approaches to this important clinical problem.hormones; muscle atrophy SKELETAL MUSCLE SERVES TWO essential functions, a contractile function for locomotion/maintenance of posture and a metabolic function as the protein reservoir of the body. The myofibers that make up the muscle consist primarily of myofibrillar proteins. The ability of the body to maintain posture or to move arises from the precise organization of myofibrillar proteins into a contractile unit called the sarcomere. The sarcomere consists of thick filaments containing primarily myosin that can slide over thin filaments containing primarily actin. Both types of filaments contain additional regulatory proteins and are linked to the ␣-actinin-containing Z disk, the thin filaments directly so and the thick filaments via titin. Vimentin and desmin are intermediate filaments that serve to anchor sarcomeres properly at the Z disks. These myofibrillar proteins, as well as the sarcoplasmic proteins, also serve as the protein reservoir of the body. Upon fasting, once hepatic glycogen stores are depleted, muscle protein degradation must be activated to provide amino acids to the liver for gluconeogenesis. These amino a...

show abstract

“…In addition, most of the genes downregulated and several genes upregulated during unloading return to basal levels within a few hours of recovery (78). These effects result in relatively rapid recovery of the fiber cross-sectional area (135,138) and muscle mass (15,(136)(137)(138)(139)(140)(141).…”

Section: 1) Myofiber Damage and Recovery Of Muscle Massmentioning

confidence: 99%

“…In addition, others have demonstrated that the downstream pathway of Akt, including ribosomal protein S6, is activated early in recovery from disuse muscle (soleus) atrophy, suggesting that the recovery of atrophied muscles is facilitated by increased mRNA translation during the early stages of resumption of loading (140). Moreover, another study concluded that a 2-wk recovery period from nonweight bearing significantly increases the activation levels of S6K and ribosomal protein S6 in medial gastrocnemius muscles of sham-operated (ovariectomy) rats, but does not influence appreciably the levels of phosphorylated Akt or mTOR in the same animals (141).…”

Section: 2) Reactivation Of the Protein Synthetic Machinerymentioning

confidence: 99%

Determinants of Disuse-Induced Skeletal Muscle Atrophy: Exercise and Nutrition Countermeasures to Prevent Protein Loss

Bajotto

Shimomura

2006

J Nutr Sci Vitaminol

View full text Add to dashboard Cite

Summary Muscle atrophy results from a variety of conditions such as disease states, neuromuscular injuries, disuse, and aging. Absence of gravitational loading during spaceflight or long-term bed rest predisposes humans to undergo substantial loss of muscle mass and, consequently, become unfit and/or unhealthy. Disuse-or inactivity-induced skeletal muscle protein loss takes place by differential modulation of proteolytic and synthetic systems. Transcriptional, translational, and posttranslational events are involved in the regulation of protein synthesis and degradation in myofibers, and these regulatory events are known to be responsive to contractile activity. However, regardless of the numerous studies which have been performed, the intracellular signals that mediate skeletal muscle wasting due to muscular disuse are not completely comprehended. Understanding the triggers of atrophy and the mechanisms that regulate protein loss in unloaded muscles may lead to the development of effective countermeasures such as exercise and dietary intervention. The objective of the present review is to provide a window into the molecular processes that underlie skeletal muscle remodeling and to examine what we know about exercise and nutrition countermeasures designed to minimize muscle atrophy. Key Words Skeletal muscle disuse atrophy, microgravity, hindlimb suspension, protein synthesis and degradation, exercise and nutrition countermeasures Because skeletal muscle is the most abundant tissue of the human body, we may hypothesize that decreases in its mass possibly will profoundly impact the wholebody metabolism and ultimately lead to the development of lifestyle-related diseases. In addition, muscle deconditioning (reduced strength, abnormal reflex patterns, increased fatigability) could limit the ability of astronauts to work in space and/or to rapidly egress the spacecraft in an emergency landing ( 1 ). Even though various functional and morphological alterations are noticeable in inactive muscles, decreased protein content has been regarded as the hallmark of skeletal muscle atrophy. Muscle protein can be either gained or lost by relative changes in protein synthesis and degradation rates, which are known to be modulated by contractile activity. Thus, understanding about the molecular regulators of protein turnover during different mechanical loading conditions and their response to specific treatments leads to the likelihood of developing effective countermeasures for preventing disuseinduced muscle wasting.This article provides a review of muscular adaptations to disuse, with emphasis on protein kinetics. We describe first the general aspects of muscle wasting with regard to exposure to actual or ground-based, simulated microgravity and some of the most significant findings that provide evidence for a close connection between skeletal muscle plasticity and protein metabolism. Next, we present a review of the literature in which results of measurements of protein synthesis/ degradation rates during unloading are avail...

show abstract

Changes in PKB/Akt and calcineurin signaling during recovery in atrophied soleus muscle induced by unloading

Abstract: . Changes in PKB/Akt and calcineurin signaling during recovery in atrophied soleus muscle induced by unloading.

Cited by 65 publications

References 34 publications

Myogenic differentiation during regrowth of atrophied skeletal muscle is associated with inactivation of GSK-3β

Myogenic differentiation during regrowth of atrophied skeletal muscle is associated with inactivation of GSK-3β

The ubiquitin proteasome system in atrophying skeletal muscle: roles and regulation

Determinants of Disuse-Induced Skeletal Muscle Atrophy: Exercise and Nutrition Countermeasures to Prevent Protein Loss

Contact Info

Product

Resources

About