Alpha-actin and cytochrome c mRNAs in atrophied adult rat skeletal muscle

1988 ◽  
Vol 254 (5) ◽  
pp. C651-C656 ◽  
Author(s):  
P. Babij ◽  
F. W. Booth
Keyword(s):  
Skeletal Muscle ◽  
Cytochrome C ◽  
Muscle Atrophy ◽  
Weight Bearing ◽  
Skeletal Muscle Atrophy ◽  
Rna Content ◽  
Mrna Content ◽  
Fast Twitch Muscle ◽  
Alpha Actin ◽  
Fast Twitch

Specific complementary DNA (cDNA) hybridization probes were used to estimate the levels of alpha-actin and cytochrome c mRNAs and also 18S rRNA in three models of skeletal muscle atrophy. After 7 days of hindlimb suspension, or immobilization, or denervation, protein content decreased 26-32% in all muscles studied except suspended fast-twitch muscle, which lost only half as much protein. alpha-Actin mRNA content decreased 51-66% and cytochrome c mRNA content decreased 42-61% in slow- and fast-twitch muscles in all three models of atrophy. However, total RNA content did not show similar directional changes; RNA content decreased 27-44% in suspended and immobilized muscle but was unchanged in denervated fast-twitch muscle. The results were interpreted to suggest that loss of weight-bearing function of skeletal muscle is a major factor affecting the levels of alpha-actin and cytochrome c mRNAs during muscle atrophy.

Overexpression of IGF-I in skeletal muscle of transgenic mice does not prevent unloading-induced atrophy

1998 ◽  
Vol 275 (3) ◽  
pp. E373-E379 ◽  
Author(s):  
David S. Criswell ◽  
Frank W. Booth ◽  
Franco DeMayo ◽  
Robert J. Schwartz ◽  
Scott E. Gordon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transgenic Mice ◽  
Weight Bearing ◽  
Mrna Level ◽  
Hindlimb Unloading ◽  
Skeletal Muscle Atrophy ◽  
Igf I ◽  
Fast Twitch Muscle ◽  
High Level ◽  
Fast Twitch

This study examined the association between local insulin-like growth factor I (IGF-I) overexpression and atrophy in skeletal muscle. We hypothesized that endogenous skeletal muscle IGF-I mRNA expression would decrease with hindlimb unloading (HU) in mice, and that transgenic mice overexpressing human IGF-I (hIGF-I) specifically in skeletal muscle would exhibit less atrophy after HU. Male transgenic mice and nontransgenic mice from the parent strain (FVB) were divided into four groups ( n = 10/group): 1) transgenic, weight-bearing (IGF-I/WB); 2) transgenic, hindlimb unloaded (IGF-I/HU); 3) nontransgenic, weight-bearing (FVB/WB); and 4) nontransgenic, hindlimb unloaded (FVB/HU). HU groups were hindlimb unloaded for 14 days. Body mass was reduced ( P < 0.05) after HU in both IGF-I (−9%) and FVB mice (−13%). Contrary to our hypothesis, we found that the relative abundance of mRNA for the endogenous rodent IGF-I (rIGF-I) was unaltered by HU in the gastrocnemius (GAST) muscle of wild-type FVB mice. High-level expression of hIGF-I peptide and mRNA was confirmed in the GAST and tibialis anterior (TA) muscles of the transgenic mice. Nevertheless, masses of the GAST and TA muscles were reduced ( P < 0.05) in both FVB/HU and IGF-I/HU groups compared with FVB/WB and IGF-I/WB groups, respectively, and the percent atrophy in mass of these muscles did not differ between FVB and IGF-I mice. Therefore, skeletal muscle atrophy may not be associated with a reduction of endogenous rIGF-I mRNA level in 14-day HU mice. We conclude that high local expression of hIGF-I mRNA and peptide in skeletal muscle alone cannot attenuate unloading-induced atrophy of fast-twitch muscle in mice.

Resistance exercise and growth hormone as countermeasures for skeletal muscle atrophy in hindlimb-suspended rats

1994 ◽  
Vol 267 (2) ◽  
pp. R365-R371 ◽  
Author(s):  
J. K. Linderman ◽  
K. L. Gosselink ◽  
F. W. Booth ◽  
V. R. Mukku ◽  
R. E. Grindeland
Keyword(s):  
Skeletal Muscle ◽  
Growth Hormone ◽  
Resistance Exercise ◽  
Protein Content ◽  
Muscle Atrophy ◽  
Myofibrillar Protein ◽  
Hindlimb Suspension ◽  
Skeletal Muscle Atrophy ◽  
Plantar Flexor ◽  
Fast Twitch

Unweighting of rat hindlimb muscles results in skeletal muscle atrophy, decreased protein synthesis, and reduced growth hormone (GH) secretion. Resistance exercise (ladder climbing) and GH treatment partially attenuate skeletal muscle atrophy in hypophysectomized hindlimb-suspended rats. It was hypothesized that a combination of multiple bouts of daily resistance exercise and GH (1 mg.kg-1.day-1) would prevent skeletal muscle atrophy in growing nonhypophysectomized hindlimb-suspended rats. Hindlimb suspension decreased the absolute (mg/pair) and relative (mg/100 g body wt) weights of the soleus, a slow-twitch plantar flexor, by 30 and 21%, respectively, and the absolute and relative weights of the gastrocnemius, a predominantly fast-twitch plantar flexor, by 20 and 11%, respectively (P < 0.05). Exercise did not increase soleus mass but attenuated loss of relative wet weight in the gastrocnemius muscles of hindlimb-suspended rats (P < 0.05). Hindlimb suspension decreased gastrocnemius myofibrillar protein content and synthesis (mg/day) by 26 and 64%, respectively (P < 0.05). The combination of exercise and GH attenuated loss of gastrocnemius myofibrillar protein content and synthesis by 70 and 23%, respectively (P < 0.05). Results of the present investigation indicate that a combination of GH and resistance exercise attenuates atrophy of unweighted fast-twitch skeletal muscles.

AMP-activated protein kinase agonists increase mRNA content of the muscle-specific ubiquitin ligases MAFbx and MuRF1 in C2C12 cells

2007 ◽  
Vol 292 (6) ◽  
pp. E1555-E1567 ◽  
Author(s):  
Brian J. Krawiec ◽  
Gerald J. Nystrom ◽  
Robert A. Frost ◽  
Leonard S. Jefferson ◽  
Charles H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Mrna Expression ◽  
Muscle Atrophy ◽  
Ubiquitin Ligases ◽  
C2c12 Cells ◽  
Skeletal Muscle Atrophy ◽  
Compound C ◽  
Mrna Content ◽  
Amp Activated Protein Kinase

The hypothesis of the present study was that exposure of differentiated muscle cells to agonists of the AMP-activated protein kinase (AMPK) would increase the mRNA content of the muscle-specific ubiquitin ligases muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1). C2C12 cells were incubated with incremental doses of 5-aminoimidazol-4-carboximide ribonucleoside (AICAR) or metformin for 24 h. Both MAFbx and MuRF1 mRNA increased dose dependently in response to these AMPK activators. AICAR, metformin, and 2-deoxy-d-glucose produced time-dependent alterations in ubiquitin ligase expression, typified by a biphasic pattern of expression marked by an acute repression followed by a sustained induction. AMPK-activating treatments in conjunction with dexamethasone produced a pronounced synergistic effect on ligase mRNA expression at later time points. This cooperative response occurred in the absence of a dexamethasone-dependent increase in AMPK expression or activity, as determined by immunoblotting for phosphorylation and expression of AMPKα and its downstream target acetyl-CoA carboxylase (ACC). These responses elicited by AMPK activation singly or in combination with dexamethasone did not extend to the mRNA expression of the UBR box family E3s UBR1/E3αI and UBR2/E3αII. Treatment with the AMPK inhibitor compound C prevented increases in MAFbx and MuRF1 mRNA in response to serum deprivation, as well as AICAR and dexamethasone treatment individually or jointly. Stimulation of AMPK activity in vivo via AICAR injection increased both MAFbx and MuRF1 mRNA in murine skeletal muscle. These data suggest that activation of AMPK in skeletal muscle results in a specific upregulation of MAFbx and MuRF1, responses that are reminiscent of the proposed atrophic transcriptional program executed under various conditions of skeletal muscle wasting. Therefore, AMPK may be a critical component of the intercalated network of signaling pathways governing skeletal muscle atrophy, where its input acts to modify anti- and proatrophic signals to influence gene expression in reaction to catabolic perturbations.

scholarly journals UBE2L3, a Partner of MuRF1/TRIM63, Is Involved in the Degradation of Myofibrillar Actin and Myosin

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1974
Author(s):  
Dulce Peris-Moreno ◽  
Mélodie Malige ◽  
Agnès Claustre ◽  
Andrea Armani ◽  
Cécile Coudy-Gandilhon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Ubiquitin Proteasome System ◽  
Contractile Proteins ◽  
Skeletal Muscle Atrophy ◽  
C2c12 Myotubes ◽  
Skeletal Muscle Wasting ◽  
Life Prognosis ◽  
Ubiquitin Conjugating Enzymes ◽  
Alpha Actin

The ubiquitin proteasome system (UPS) is the main player of skeletal muscle wasting, a common characteristic of many diseases (cancer, etc.) that negatively impacts treatment and life prognosis. Within the UPS, the E3 ligase MuRF1/TRIM63 targets for degradation several myofibrillar proteins, including the main contractile proteins alpha-actin and myosin heavy chain (MHC). We previously identified five E2 ubiquitin-conjugating enzymes interacting with MuRF1, including UBE2L3/UbcH7, that exhibited a high affinity for MuRF1 (KD = 50 nM). Here, we report a main effect of UBE2L3 on alpha-actin and MHC degradation in catabolic C2C12 myotubes. Consistently UBE2L3 knockdown in Tibialis anterior induced hypertrophy in dexamethasone (Dex)-treated mice, whereas overexpression worsened the muscle atrophy of Dex-treated mice. Using combined interactomic approaches, we also characterized the interactions between MuRF1 and its substrates alpha-actin and MHC and found that MuRF1 preferentially binds to filamentous F-actin (KD = 46.7 nM) over monomeric G-actin (KD = 450 nM). By contrast with actin that did not alter MuRF1–UBE2L3 affinity, binding of MHC to MuRF1 (KD = 8 nM) impeded UBE2L3 binding, suggesting that differential interactions prevail with MuRF1 depending on both the substrate and the E2. Our data suggest that UBE2L3 regulates contractile proteins levels and skeletal muscle atrophy.

Daily running for 2 wk and mRNAs for cytochrome c and alpha-actin in rat skeletal muscle

1989 ◽  
Vol 257 (5) ◽  
pp. C936-C939 ◽  
Author(s):  
P. R. Morrison ◽  
R. B. Biggs ◽  
F. W. Booth
Keyword(s):  
Skeletal Muscle ◽  
Cytochrome C ◽  
Training Program ◽  
Citrate Synthase ◽  
Mitochondrial Protein ◽  
Female Rats ◽  
Hindlimb Muscles ◽  
Actin Mrna ◽  
Alpha Actin ◽  
Fast Twitch

The purpose of the study was to determine whether daily running durations that were 7-14% of the durations employed in the chronic stimulation protocols (consisting of 24 h of daily indirect electrical stimulation of skeletal muscles) still resulted in increases in a mitochondrial protein mRNA. Adult female rats were run 100 min/day on motor-driven treadmills for 2 wk. Documentation that rats underwent the stated training program was obtained by a 30-41% increase in citrate synthase activity in hindlimb muscles after 2 wk of the training. Cytochrome c mRNA was increased 17-56% in hindlimb muscles after the 2-wk training program. Thus shorter durations of exercise (100 min/day rather than 24 h/day) can increase cytochrome c mRNA. alpha-Actin mRNA increased 61-62% in fast-twitch muscles in the hindlimbs of the same rats that underwent the 2 wk of run training but did not increase in the predominantly slow-twitch soleus muscle. The increase in alpha-actin mRNA was unexpected, since it is well known that this type of physical exercise does not increase the size of fast-twitch skeletal muscle.

Role for IκBα, but not c-Rel, in skeletal muscle atrophy

2007 ◽  
Vol 292 (1) ◽  
pp. C372-C382 ◽  
Author(s):  
Andrew R. Judge ◽  
Alan Koncarevic ◽  
R. Bridge Hunter ◽  
Hsiou-Chi Liou ◽  
Robert W. Jackman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Target Genes ◽  
Weight Bearing ◽  
Family Members ◽  
Dominant Negative ◽  
Hindlimb Unloading ◽  
Skeletal Muscle Atrophy ◽  
Significant Advance ◽  
Protein Ubiquitination

Skeletal muscle atrophy is associated with a marked and sustained activation of nuclear factor-κB (NF-κB) activity. Previous work showed that p50 is one of the NF-κB family members required for this activation and for muscle atrophy. In this work, we tested whether another NF-κB family member, c-Rel, is required for atrophy. Because endogenous inhibitory factor κBα (IκBα) was activated (i.e., decreased) at 3 and 7 days of muscle disuse (i.e., hindlimb unloading), we also tested if IκBα, which binds and retains Rel proteins in the cytosol, is required for atrophy and intermediates of the atrophy process. To do this, we electrotransferred a dominant negative IκBα (IκBαΔN) in soleus muscles, which were either unloaded or weight bearing. IκBαΔN expression abolished the unloading-induced increase in both NF-κB activation and total ubiquitinated protein. IκBαΔN inhibited unloading-induced fiber atrophy by 40%. The expression of certain genes known to be upregulated with atrophy were significantly inhibited by IκBαΔN expression during unloading, including MAFbx/atrogin-1, Nedd4, IEX, 4E-BP1, FOXO3a, and cathepsin L, suggesting these genes may be targets of NF-κB transcription factors. In contrast, c-Rel was not required for atrophy because the unloading-induced markers of atrophy were the same in c-rel−/− and wild-type mice. Thus IκBα degradation is required for the unloading-induced decrease in fiber size, the increase in protein ubiquitination, activation of NF-κB signaling, and the expression of specific atrophy genes, but c-Rel is not. These data represent a significant advance in our understanding of the role of NF-κB/IκB family members in skeletal muscle atrophy, and they provide new candidate NF-κB target genes for further study.

scholarly journals NF-κB but not FoxO sites in the MuRF1 promoter are required for transcriptional activation in disuse muscle atrophy

2014 ◽  
Vol 306 (8) ◽  
pp. C762-C767 ◽  
Author(s):  
Chia-Ling Wu ◽  
Evangeline W. Cornwell ◽  
Robert W. Jackman ◽  
Susan C. Kandarian
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Transcriptional Activation ◽  
Weight Bearing ◽  
Gene Activation ◽  
Hindlimb Unloading ◽  
Skeletal Muscle Atrophy ◽  
Luciferase Reporter ◽  
Disuse Atrophy

The muscle-specific ring finger protein 1 (MuRF1) gene is required for most types of skeletal muscle atrophy yet we have little understanding of its transcriptional regulation. The purpose of this study is to identify whether NF-κB and/or FoxO response elements in the MuRF1 promoter are required for MuRF1 gene activation during skeletal muscle atrophy due to the removal of hindlimb weight bearing (“unloading”). Both NF-κB -dependent and FoxO-dependent luciferase reporter activities were significantly increased at 5 days of unloading. Using a 4.4-kb MuRF1 promoter reporter construct, a fourfold increase in reporter (i.e., luciferase) activity was found in rat soleus muscles after 5 days of hindlimb unloading. This activation was abolished by mutagenesis of either of the two distal putative NF-κB sites or all three putative NF-κB sites but not by mutagenesis of all four putative FoxO sites. This work provides the first direct evidence that NF-κB sites, but not FoxO sites, are required for MuRF1 promoter activation in muscle disuse atrophy in vivo.

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