Competitive control of myosin expression: hypertrophy vs. hyperthyroidism

1991 ◽  
Vol 70 (5) ◽  
pp. 2328-2330 ◽  
Author(s):  
C. D. Ianuzzo ◽  
N. Hamilton ◽  
B. Li
Keyword(s):  
Skeletal Muscle ◽  
Phenotypic Expression ◽  
Compensatory Hypertrophy ◽  
Surgical Removal ◽  
Type I ◽  
Myosin Isoforms ◽  
Skeletal Muscle Myosin ◽  
Slow Myosin ◽  
Fast Myosin ◽  
Muscle Myosin

The competition between two opposing influences on the phenotypic expression of skeletal muscle myosin were studied to determine which was the dominant regulator. Experimental hyperthyroidism, which induces fast myosin expression, was produced by subcutaneous implantation of a 40-day constant-time-release triiodothyronine pellet. Compensatory hypertrophy, which induces slow myosin expression, was produced by surgical removal of a synergistic hindlimb muscle. Hyperthyroidism increased the percentage of type II fibers and the fast myosin isoforms in both the plantaris and soleus muscles. Hypertrophy significantly increased the percentage of type I fibers and the slow myosin type in the plantaris and soleus muscles. However, with the simultaneous introduction of hyperthyroidism and hypertrophy, only the hyperthyroid effects were observed. Hyperthyroidism and not physiological demand was found to be the dominant regulator of skeletal muscle myosin expression.

Interaction of thyroid hormone and functional overload on skeletal muscle isomyosin expression

1994 ◽  
Vol 77 (2) ◽  
pp. 621-629 ◽  
Author(s):  
S. J. Swoap ◽  
F. Haddad ◽  
V. J. Caiozzo ◽  
R. E. Herrick ◽  
S. A. McCue ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Normal Control ◽  
Mrna Level ◽  
Control Group ◽  
Surgical Removal ◽  
Type I ◽  
Overload Control ◽  
Skeletal Muscle Myosin ◽  
Protein Response

This study examined the interaction of exogenous thyroid hormone 3,5,3′-triiodothyronine (T3) and functional overload on skeletal muscle myosin heavy chain (MHC) expression, studied at both the protein and mRNA level of analysis. Animals were allocated to the following groups: 1) normal control, 2) overload control, 3) hyperthyroid control, and 4) hyperthyroid+overload. Overload of the rat plantaris was accomplished by surgical removal of its synergists (soleus and gastrocnemius), and the animals were made hyperthyroid by injections of T3 (350 micrograms/kg every other day). After overload of 8 wk, muscle enlargement occurred by 53% for both overload groups (P < 0.05). This was accompanied by a 330 and 82% increase in the relative content of type I and IIa MHC, respectively, and a corresponding decrease by 16 and 44% in type IIx and IIb MHC, respectively, in the overload control group (P < 0.05 vs. normal control). Changes in the relative and absolute content of mRNA for these MHCs paralleled the protein response. Exogenous T3 completely reversed the upregulation of type I MHC and the downregulation of type IIx associated with overload at both the protein and mRNA level (P < 0.05). However, T3 was only partially effective in blunting the downregulation of IIb MHC and the upregulation of IIa MHC (protein and mRNA) accompanying the overload.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Glycine 699 is pivotal for the motor activity of skeletal muscle myosin.

1996 ◽  
Vol 134 (4) ◽  
pp. 895-909 ◽  
Author(s):  
F Kinose ◽  
S X Wang ◽  
U S Kidambi ◽  
C L Moncman ◽  
D A Winkelmann
Keyword(s):  
Skeletal Muscle ◽  
Motor Activity ◽  
Expression System ◽  
Motor Domain ◽  
C2c12 Cells ◽  
Myosin Isoforms ◽  
Skeletal Muscle Myosin ◽  
Lever Arm ◽  
Wide Range ◽  
Muscle Myosin

Myosin couples ATP hydrolysis to the translocation of actin filaments to power many forms of cellular motility. A striking feature of the structure of the muscle myosin head domain is a 9-nm long "lever arm" that has been postulated to produce a 5-10-nm power stroke. This motion must be coupled to conformational changes around the actin and nucleotide binding sites. The linkage of these sites to the lever arm has been analyzed by site-directed mutagenesis of a conserved glycine residue (G699) found in a bend joining two helices containing the highly reactive and mobile cysteine residues, SH1 and SH2. Alanine mutagenesis of this glycine (G699A) dramatically alters the motor activity of skeletal muscle myosin, inhibiting the velocity of actin filament movement by &gt; 100-fold. Analysis of the defect in the G699A mutant myosin is consistent with a marked slowing of the transition within the motor domain from a strong binding to a weak binding interaction with actin. This result is interpreted in terms of the role of this residue (G699) as a pivot point for motion of the lever arm. The recombinant myosin used in these experiments has been produced in a unique expression system. A shuttle vector containing a regulated muscle-specific promoter has been developed for the stable expression of recombinant myosin in C2C12 cells. The vector uses the promoter/enhancer region, the first two and the last five exons of an embryonic rat myosin gene, to regulate the expression of an embryonic chicken muscle myosin cDNA. Stable cell lines transfected with this vector express the unique genetically engineered myosin after differentiation into myotubes. The myosin assembles into myofibrils, copurifies with the endogenous myosin, and contains a complement of muscle-specific myosin light chains. The functional activity of the recombinant myosin is readily analyzed with an in vitro motility assay using a species-specific anti-S2 mAb to selectively assay the recombinant protein. This expression system has facilitated manipulation and analysis of the skeletal muscle myosin motor domain and is also amenable to a wide range of structure-function experiments addressing questions unique to the muscle-specific cytoarchitecture and myosin isoforms.

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