scholarly journals Mutation of the IIB myosin heavy chain gene results in muscle fiber loss and compensatory hypertrophy

2001 ◽  
Vol 280 (3) ◽  
pp. C637-C645 ◽  
Author(s):  
David L. Allen ◽  
Brooke C. Harrison ◽  
Carol Sartorius ◽  
William C. Byrnes ◽  
Leslie A. Leinwand
Keyword(s):  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Body Mass ◽  
Heavy Chain ◽  
Compensatory Hypertrophy ◽  
Muscle Disease ◽  
Chain Gene ◽  
Fiber Types ◽  
Mouse Skeletal Muscle ◽  
Ultrastructural Studies

The fast skeletal IIb gene is the source of most myosin heavy chain (MyHC) in adult mouse skeletal muscle. We have examined the effects of a null mutation in the IIb MyHC gene on the growth and morphology of mouse skeletal muscle. Loss in muscle mass of several head and hindlimb muscles correlated with amounts of IIb MyHC expressed in that muscle in wild types. Decreased mass was accompanied by decreases in mean fiber number, and immunological and ultrastructural studies revealed fiber pathology. However, mean cross-sectional area was increased in all fiber types, suggesting compensatory hypertrophy. Loss of muscle and body mass was not attributable to impaired chewing, and decreased food intake as a softer diet did not prevent the decrease in body mass. Thus loss of the major MyHC isoform produces fiber loss and fiber pathology reminiscent of muscle disease.

Kinetic properties of myosin heavy chain isoforms in mouse skeletal muscle: comparison with rat, rabbit, and human and correlation with amino acid sequence

2004 ◽  
Vol 287 (6) ◽  
pp. C1725-C1732 ◽  
Author(s):  
Oleg Andruchov ◽  
Olena Andruchova ◽  
Yishu Wang ◽  
Stefan Galler
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Actin Binding ◽  
Kinetic Properties ◽  
Fiber Types ◽  
Mouse Skeletal Muscle ◽  
Structural Variability ◽  
Kinetics Of

Stretch activation kinetics were investigated in skinned mouse skeletal muscle fibers of known myosin heavy chain (MHC) isoform content to assess kinetic properties of different myosin heads while generating force. The time to peak of stretch-induced delayed force increase ( t3) was strongly correlated with MHC isoforms [ t3 given in ms for fiber types containing specified isoforms; means ± SD with n in parentheses: MHCI 680 ± 108 ( 13 ), MHCIIa 110.5 ± 10.7 ( 23 ), MHCIIx(d) 46.2 ± 5.2 ( 20 ), MHCIIb 23.5 ± 3.3 (76)]. This strong correlation suggests different kinetics of force generation of different MHC isoforms in the following order:MHCIIb > MHCIIx(d) > MHCIIa ≫ MHCI. For rat, rabbit, and human skeletal muscles the same type of correlation was found previously. The kinetics decreases slightly with increasing body mass. Available amino acid sequences were aligned to quantify the structural variability of MHC isoforms of different animal species. The variation in t3 showed a correlation with the structural variability of specific actin-binding loops (so-called loop 2 and loop 3) of myosin heads ( r = 0.74). This suggests that alterations of amino acids in these loops contribute to the different kinetics of myosin heads of various MHC isoforms.

scholarly journals Calcineurin plays a modulatory role in loading-induced regulation of type I myosin heavy chain gene expression in slow skeletal muscle

2009 ◽  
Vol 297 (4) ◽  
pp. R1037-R1048 ◽  
Author(s):  
Clay E. Pandorf ◽  
Weihua H. Jiang ◽  
Anqi X. Qin ◽  
Paul W. Bodell ◽  
Kenneth M. Baldwin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Fiber Type ◽  
Hindlimb Suspension ◽  
Chain Gene ◽  
Type I ◽  
Thyroid State

The role of calcineurin (Cn) in skeletal muscle fiber-type expression has been a subject of great interest because of reports indicating that it controls the slow muscle phenotype. To delineate the role of Cn in phenotype remodeling, particularly its role in driving expression of the type I myosin heavy chain (MHC) gene, we used a novel strategy whereby a profound transition from fast to slow fiber type is induced and examined in the absence and presence of cyclosporin A (CsA), a Cn inhibitor. To induce the fast-to-slow transition, we first subjected rats to 7 days of hindlimb suspension (HS) + thyroid hormone [triiodothyronine (T3)] to suppress nearly all expression of type I MHC mRNA in the soleus muscle. HS + T3 was then withdrawn, and rats resumed normal ambulation and thyroid state, during which vehicle or CsA (30 mg·kg−1·day−1) was administered for 7 or 14 days. The findings demonstrate that, despite significant inhibition of Cn, pre-mRNA, mRNA, and protein abundance of type I MHC increased markedly during reloading relative to HS + T3 ( P < 0.05). Type I MHC expression was, however, attenuated by CsA compared with vehicle treatment. In addition, type IIa and IIx MHC pre-mRNA, mRNA, and relative protein levels were increased in Cn-treated compared with vehicle-treated rats. These findings indicate that Cn has a modulatory role in MHC transcription, rather than a role as a primary regulator of slow MHC gene expression.

Function Of Natural Antisense RNA In Coordinating Myosin Heavy Chain Gene Switching In Skeletal Muscle

2005 ◽  
Vol 37 (Supplement) ◽  
pp. S245???S246 ◽  
Author(s):  
Clay E. Pandorf ◽  
Faddia Haddad ◽  
Roland R. Roy ◽  
Anqi X. Qin ◽  
V. Reggie Edgerton ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Antisense Rna ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Myosin Heavy Chain Gene ◽  
Natural Antisense Rna ◽  
Gene Switching

scholarly journals Mutated WWP1 Induces an Aberrant Expression of Myosin Heavy Chain Gene in C2C12 Skeletal Muscle Cells

2010 ◽  
Vol 47 (2) ◽  
pp. 115-119 ◽  
Author(s):  
Hirokazu Matsumoto ◽  
Yumi Inba ◽  
Shinji Sasazaki ◽  
Akira Fujiwara ◽  
Nobutsune Ichihara ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Myosin Heavy Chain Gene ◽  
Aberrant Expression ◽  
C2c12 Skeletal Muscle Cells

Skeletal muscle myosin heavy chain isoforms and energy metabolism after clenbuterol treatment in the rat

2000 ◽  
Vol 279 (3) ◽  
pp. R1076-R1081 ◽  
Author(s):  
P. Rajab ◽  
J. Fox ◽  
S. Riaz ◽  
D. Tomlinson ◽  
D. Ball ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Myosin Heavy Chain ◽  
Body Mass ◽  
Heavy Chain ◽  
Adenine Nucleotide ◽  
Prolonged Treatment ◽  
Skeletal Muscle Myosin ◽  
Adenine Nucleotide Pool ◽  
Muscle Myosin

Prolonged treatment with the β2-adrenoceptor agonist clenbuterol (1–2 mg · kg body mass−1 · day −1) is known to induce the hypertrophy of fast-contracting fibers and the conversion of slow- to fast-contracting fibers. We investigated the effects of administering a lower dose of clenbuterol (250 μg · kg body mass−1 · day−1) on skeletal muscle myosin heavy chain (MyHC) protein isoform content and adenine nucleotide (ATP, ADP, and AMP) concentrations. Male Wistar rats were administered clenbuterol ( n = 8) or saline ( n = 6) subcutaneously for 8 wk, after which the extensor digitorum longus (EDL) and soleus muscles were removed. We demonstrated an increase of type IIa MyHC protein content in the soleus from ∼0.5% in controls to ∼18% after clenbuterol treatment ( P < 0.05), which was accompanied by an increase in the total adenine nucleotide pool (TAN; ∼19%, P < 0.05) and energy charge [E-C = (ATP + 0.5 ADP)/(ATP + ADP + AMP); ∼4%; P < 0.05]. In the EDL, a reduction in the content of the less prevalent type I MyHC protein from ∼3% in controls to 0% after clenbuterol treatment ( P < 0.05) occurred without any alterations in TAN and E-C. These findings demonstrate that the phenotypic changes previously observed in slow muscle after clenbuterol administration at 1–2 mg · kg body mass−1 · day−1 are also observed at a substantially lower dose and are paralleled by concomitant changes in cellular energy metabolism.

Effect of endurance exercise on myosin heavy chain gene regulation in human skeletal muscle

1999 ◽  
Vol 276 (2) ◽  
pp. R414-R419 ◽  
Author(s):  
D. Sean O’Neill ◽  
Donghai Zheng ◽  
Wade K. Anderson ◽  
G. Lynis Dohm ◽  
Joseph A. Houmard
Keyword(s):  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Human Skeletal Muscle ◽  
Contractile Activity ◽  
Maximal Oxygen Consumption ◽  
Exercise Bout ◽  
Cycle Ergometer ◽  
Chain Gene ◽  
Exercise Period

The purpose of this study was to determine the effect of endurance-oriented exercise on myosin heavy chain (MHC) isoform regulation in human skeletal muscle. Exercise consisted of 1 h of cycle ergometer work per day at 75% maximal oxygen consumption for seven consecutive days. Muscle was obtained before the first bout of exercise, 3 h after the first bout of exercise, and before and 3 h after the final exercise bout on day 7( n = 9 subjects). No changes in MHC mRNA (I, IIa, IIx) were evident after the first exercise period. There was, however, a significant ( P < 0.05) decline (−30%) in MHC IIx mRNA 3 h after the final training bout. An interesting finding was that a higher pretraining level of MHC IIx mRNA was associated with a greater decline in the transcript before ( r = 0.68, P < 0.05) and 3 h after ( r = 0.82, P < 0.05) the final exercise bout. These findings suggest that MHC IIx mRNA is downregulated during the early phase of endurance-oriented exercise training in human skeletal muscle but only after repeated contractile activity. Pretraining MHC IIx mRNA content may influence the magnitude of this response.

scholarly journals Evidence of MyomiR network regulation of β-myosin heavy chain gene expression during skeletal muscle atrophy

2009 ◽  
Vol 39 (3) ◽  
pp. 219-226 ◽  
Author(s):  
John J. McCarthy ◽  
Karyn A. Esser ◽  
Charlotte A. Peterson ◽  
Esther E. Dupont-Versteegden
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Heavy Chain ◽  
Hindlimb Suspension ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Myosin Heavy Chain Gene

There is a growing recognition that noncoding RNAs (ncRNA) play an important role in the regulation of gene expression. A class of small (19–22 nt) ncRNAs, known as microRNAs (miRs), have received a great deal of attention lately because of their ability to repress gene expression through a unique posttranscriptional 3′-untranslated region (UTR) mechanism. The objectives of the current study were to identify miRs expressed in the rat soleus muscle and determine if their expression was changed in response to hindlimb suspension. Comprehensive profiling revealed 151 miRs were expressed in the soleus muscle and expression of 18 miRs were significantly ( P < 0.01) changed after 2 and/or 7 days of hindlimb suspension. The significant decrease (16%) in expression of muscle-specific miR-499 in response to hindlimb suspension was confirmed by RT-PCR and suggested activation of the recently proposed miR encoded by myosin gene (MyomiR) network during atrophy. Further analysis of soleus muscle subjected to hindlimb suspension for 28 days provided evidence consistent with MyomiR network repression of β-myosin heavy chain gene (β-MHC) expression. The significant downregulation of network components miR-499 and miR-208b by 40 and 60%, respectively, was associated with increased expression of Sox6 (2.2-fold) and Purβ (23%), predicted target genes of miR-499 and known repressors of β-MHC expression. A Sox6 3′-UTR reporter gene confirmed Sox6 is a target gene of miR-499. These results further expand the role of miRs in adult skeletal muscle and are consistent with a model in which the MyomiR network regulates slow myosin expression during muscle atrophy.

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