A glimpse into the early window of muscle unloading

2021 ◽  
Author(s):  
Matthew H. Brisendine ◽  
Jacob M. Bond
Keyword(s):  
2008 ◽  
Vol 34 (2) ◽  
pp. 149-161 ◽  
Author(s):  
Dawn J. Mazzatti ◽  
Melissa A. Smith ◽  
Radu C. Oita ◽  
Fei-Ling Lim ◽  
Andrew J. White ◽  
...  

A number of physiological changes follow prolonged skeletal muscle unloading as occurs in spaceflight, bed rest, and hindlimb suspension (HLS) and also in aging. These include muscle atrophy, fiber type switching, and loss of the ability to switch between lipid and glucose usage, or metabolic inflexibility. The signaling and genomic events that precede these physiological manifestations have not been investigated in detail, particularly in regard to loss of metabolic flexibility. Here we used gene arrays to determine the effects of 24-h HLS on metabolic remodeling in mouse muscle. Acute unloading resulted in differential expression of a number of transcripts in soleus and gastrocnemius muscle, including many involved in lipid and glucose metabolism. These include the peroxisome proliferator-activated receptors (PPARs). In contrast to Ppar-α and Ppar-γ, which were downregulated by acute HLS, Ppar-δ was upregulated concomitant with increased expression of its downstream target, uncoupling protein-3 ( Ucp-3). However, differential expression of Ppar-δ was both acute and transient in nature, suggesting that regulation of PPARδ may represent an adaptive, compensatory response aimed at regulating fuel utilization and maintaining metabolic flexibility.


2003 ◽  
Vol 57 (3) ◽  
pp. 246-256 ◽  
Author(s):  
Michael R. Deschenes ◽  
Meredith H. Wilson

2019 ◽  
Vol 83 ◽  
pp. 302-313 ◽  
Author(s):  
Alix C. Deymier ◽  
Andrea G. Schwartz ◽  
Zhounghou Cai ◽  
Tyrone L. Daulton ◽  
Jill D. Pasteris ◽  
...  

Thorax ◽  
2008 ◽  
Vol 63 (10) ◽  
pp. 910-915 ◽  
Author(s):  
A Borghi-Silva ◽  
C C Oliveira ◽  
C Carrascosa ◽  
J Maia ◽  
D C Berton ◽  
...  

2003 ◽  
Vol 210 (1-2) ◽  
pp. 5-10 ◽  
Author(s):  
Michael R Deschenes ◽  
Kristin M Will ◽  
Frank W Booth ◽  
Scott E Gordon

2020 ◽  
Vol 21 (13) ◽  
pp. 4815 ◽  
Author(s):  
Ekaterina P. Mochalova ◽  
Svetlana P. Belova ◽  
Tatiana Y. Kostrominova ◽  
Boris S. Shenkman ◽  
Tatiana L. Nemirovskaya

Unloading leads to skeletal muscle atrophy via the upregulation of MuRF-1 and MAFbx E3-ligases expression. Reportedly, histone deacetylases (HDACs) 4 and 5 may regulate the expression of MuRF1 and MAFbx. To examine the HDAC-dependent mechanisms involved in the control of E3-ubiquitin ligases expression at the early stages of muscle unloading we used HDACs 4 and 5 inhibitor LMK-235 and HDAC 4 inhibitor Tasqinimod (Tq). Male Wistar rats were divided into four groups (eight rats per group): nontreated control (C), three days of unloading/hindlimb suspension (HS) and three days HS with HDACs inhibitor LMK-235 (HSLMK) or Tq (HSTq). Treatment with LMK-235 diminished unloading-induced of MAFbx, myogenin (MYOG), ubiquitin and calpain-1 mRNA expression (p < 0.05). Tq administration had no effect on the expression of E3-ligases. The mRNA expression of MuRF1 and MAFbx was significantly increased in both HS and HSTq groups (1.5 and 4.0 folds, respectively; p < 0.05) when compared with the C group. It is concluded that during three days of muscle unloading: (1) the HDACs 4 and 5 participate in the regulation of MAFbx expression as well as the expression of MYOG, ubiquitin and calpain-1; (2) the inhibition of HDAC 4 has no effect on MAFbx expression. Therefore, HDAC 5 is perhaps more important for the regulation of MAFbx expression than HDAC 4.


1989 ◽  
Vol 66 (3) ◽  
pp. 1093-1098 ◽  
Author(s):  
G. Howard ◽  
J. M. Steffen ◽  
T. E. Geoghegan

Muscle atrophy resulting from disuse is associated with marked decrements in protein synthesis. The objective of the present investigation was to determine levels of total muscle RNA and the content and composition of the mRNA fraction as a qualitative assessment of the potential regulatory role of transcriptional alterations in unloaded skeletal muscles. Hindlimb muscle unloading was produced by whole-body suspension of rats for up to 7 days. The soleus, gastrocnemius, and extensor digitorum longus (EDL) were excised from 1-, 3-, and 7-day suspended and pair-fed controls, and RNA was extracted by homogenization in 5 M guanidinium thiocyanate. Total RNA and mRNA contents were lower in soleus and gastrocnemius after 7 days of suspension compared with pair-fed controls, but total RNA and mRNA concentrations (per g muscle and per microgram total RNA, respectively) were unaltered. alpha-Actin mRNA, assessed by dot blot hybridization, was significantly reduced in soleus after 1 (37%), 3 (28%), and 7 (59%) days of suspension and in gastrocnemius after 3 (44%) and 7 (41%) days. However, alpha-actin mRNA was unchanged in the EDL after suspension. Protein synthesis directed by RNA extracted from soleus and EDL indicated marked (30–400%) alterations in mRNAs coding for several small (15- to 25-kDa) proteins. The results of this study suggest that altered transcription and availability of specific mRNAs could contribute significantly to the regulation of protein synthesis during unloading of skeletal muscle.


1998 ◽  
Vol 84 (3) ◽  
pp. 1083-1087 ◽  
Author(s):  
David S. Criswell ◽  
Vanessa R. M. Hodgson ◽  
Edna C. Hardeman ◽  
Frank W. Booth

We examined the regulation of the troponin I slow (TnIs) promoter during skeletal muscle unloading-induced protein isoform transition, by using a transgenic mouse line harboring the −4,200 to +12 base pairs region of the human TnIs promoter. Eighteen female transgenic mice (∼30 g body mass) were randomly divided into two groups: weight-bearing (WB) controls ( n = 9) and hindlimb unloaded (HU; n = 9). The HU mice were tail suspended for 7 days. Body mass was unchanged in the WB group but was reduced (−6%; P < 0.05) after the HU treatment. Absolute soleus muscle mass (−25%) and soleus mass relative to body mass (−16%) were both lower ( P < 0.05) in the HU group compared with the WB mice. Northern blot analyses indicate that 7 days of HU result in a 64% decrease ( P < 0.05) in the abundance of endogenous TnIs mRNA (μg/mg muscle) in the mouse soleus. Furthermore, there is a trend for the abundance of the fast troponin I mRNA to be increased (+34%). Analysis of transgenic chloramphenicol acetyltransferase activity in the soleus muscle revealed no difference ( P > 0.05) between WB and HU groups. We conclude that additional elements are necessary for the TnIs gene to respond to an unloading-induced, slow-to-fast isoform transition stimulus.


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