scholarly journals miR-206 enforces a slow muscle phenotype

2020 ◽  
Vol 133 (15) ◽  
pp. jcs243162
Author(s):  
Kristen K. Bjorkman ◽  
Martin G. Guess ◽  
Brooke C. Harrison ◽  
Michael M. Polmear ◽  
Angela K. Peter ◽  
...  

ABSTRACTStriated muscle is a highly specialized collection of tissues with contractile properties that vary according to functional needs. Although muscle fiber types are established postnatally, lifelong plasticity facilitates stimulus-dependent adaptation. Functional adaptation requires molecular adaptation, which is partially provided by miRNA-mediated post-transcriptional regulation. miR-206 is a muscle-specific miRNA enriched in slow muscles. We investigated whether miR-206 drives the slow muscle phenotype or is merely an outcome. We found that miR-206 expression increases in both physiological (including female sex and endurance exercise) and pathological conditions (muscular dystrophy and adrenergic agonism) that promote a slow phenotype. Consistent with that observation, the slow soleus muscle of male miR-206-knockout mice displays a faster phenotype than wild-type mice. Moreover, left ventricles of male miR-206 knockout mice have a faster myosin profile, accompanied by dilation and systolic dysfunction. Thus, miR-206 appears to be necessary to enforce a slow skeletal and cardiac muscle phenotype and to play a key role in muscle sexual dimorphisms.

2019 ◽  
Author(s):  
Kristen K. Bjorkman ◽  
Martin G. Guess ◽  
Brooke C. Harrison ◽  
Michael M. Polmear ◽  
Angela K. Peter ◽  
...  

AbstractStriated muscle is a highly specialized collection of tissues with contractile properties varying according to functional needs. Although muscle fiber types are established postnatally, lifelong plasticity facilitates stimulus-dependent adaptation. Functional adaptation requires molecular adaptation, partially provided by miRNA-mediated post-transcriptional regulation. miR-206 is a muscle-specific miRNA enriched in slow muscles. We investigated whether miR-206 drives the slow muscle phenotype or is merely an outcome. We found that miR-206 expression increases in both physiologic (including female sex and endurance exercise) and pathologic conditions that promote a slow phenotype. Consistent with that observation, the slow soleus muscle of male miR-206 knockout mice displays a faster phenotype than wild-type mice. Moreover, their left ventricles have a faster myosin profile accompanied by male-specific dilation and systolic dysfunction. Thus, miR-206 appears necessary to enforce a slow skeletal and cardiac muscle phenotype and to play a key role in muscle sexual dimorphisms.


2000 ◽  
Vol 6 (S2) ◽  
pp. 852-853
Author(s):  
Glenn M. Cohen ◽  
Margaret F. Scott

Striated skeletal muscle has been considered radioresistant because it is highly differentiated and post-mitotic. Striated muscle does, however, respond to irradiation with morphological and biochemical changes after short and long latency periods; vascular and/or neurological impairments might contribute to the delayed responses to irradiation.The objective of the present study was to determine the susceptibility of three amphibian muscle fiber types to Co60 irradiation. In amphibians, the three major fiber types are 1) large twitch fibers, which contain low levels of mitochondrial enzymes and lipids, but intermediate levels of glycogen; 2) small twitch fibers, which contain high levels of both glycolytic and mitochondrial enzymes (FIG. 1); and tonic fibers, which contain low levels of all three histochemical markers. Thus, the determination of susceptibility of different amphibian fiber types to irradiation might indicate whether the metabolic characteristics of the fibers, rather than morphological or electrical properties, could serve as an early indicator of radiation damage.


1966 ◽  
Vol 49 (6) ◽  
pp. 1177-1198 ◽  
Author(s):  
PAUL BACH-y-RITA ◽  
FUMIO ITO

In anesthetized in vivo preparations, responses of two types of extraocular muscle fibers have been studied. The small, multiply innervated slow fibers have been shown to be capable of producing propagated impulses, and thus have been labeled slow multi-innervated twitch fibers. Fast and slow multi-innervated twitch fibers are distinguished by impulse conduction velocities, by ranges of membrane potentials, by amplitudes and frequencies of the miniature end plate potentials, by responses to the intravenous administration of succinylcholine, by the frequency of stimulation required for fused tetanus, and by the velocities of conduction of the nerve fibers innervating each of the muscle fiber types.


2018 ◽  
Vol 1 (2) ◽  
Author(s):  
Can Li ◽  
Nan Li ◽  
Yong Zhang

Objective To investigate how different skeletal muscle fiber types affect development of insulin resistance, and to explore the role of mitochondrial quality control system, especially mitochondrial unfolded protein response (UPRmt) and mitophagy, in response to metabolic stresses. Methods Male Wistar rats were randomly divided into 2 groups: fed with the normal diet for 8 weeks (Con), and fed with 45% high-fat diet for 8 weeks (IR). Fasting blood glucose (FBG), fasting insulin (FIN) and oral glucose tolerance test (OGTT) were used to identify insulin resistance model. Gastrocnemius (GC), soleus (SOL) and tibialis anterior (TA) muscle were isolated, and RT-qPCR was used to determine the expression of Myhc7, Myhc4. Oxygraph-2k was used to determine the mitochondrial State 3 (ST3), State 4(ST4) respiration and respiration control rate (RCR). JC-1 probe was used to measure mitochondrial membrane potential. Western Blot was used to determine the expressions of marker proteins of muscle fiber types (Myhc4, Myhc7), UPRmt related proteins (Hsp60, Hsp70) and mitophagy related proteins (Pink1, LC3). Results Compared with Con group, in IR group, FBG (7.1±1.27 vs. 5.4±0.43,p<0.05), FIN (19.4±5.2 vs. 31.6±6.7,p<0.05 ) and OGTT (area under the curve, about 31.7% increases, p<0.05) were significantly higher. Myhc4 mRNA (relative fold about 55.6% increases) and protein expression (about 33.9% increases, p<0.05) were significantly higher in GC. Myhc4 protein expression was significantly higher in GC (about 60.5% increases, p<0.05). While Myhc7 mRNA expression (about 51.1% decreases, p<0.05) was significantly lower in SOL. Compared with Con group, in IR group, mitochondrial RCR in SOL muscle was significantly lower (about 22.5% decreases, p<0.05). Furthermore, the expression of HSP60 (about 36.7% increases,p<0.05) and HSP70 (about 44.3% increases,p<0.05) was significantly higher in TA muscle, while the expression of Parkin (about 18.8% decreases,p<0.05) and the ratio between LC3 II/I (about 26.0% decreases,p<0.05)expression in SOL muscle were significantly lower. Conclusions In this study, we found that the percentage of fast muscle fibers was elevated in IR skeletal muscle, which were supported by increased Myhc4 and decreased Myhc7 level. Impaired mitochondrial function was only observed in slow muscle as inhibition of mitochondrial respiration. As marker of UPRmt, HSP60/70 were specifically activated in fast muscle in IR, while mitophagy-related proteins were specifically increased in slow muscle. These results indicate that mitochondrial quality control systems are selectively activated to recover mitochondrial functions depending on muscle fiber types in insulin resistant rat.


2009 ◽  
Vol 385 (1) ◽  
pp. 44-48 ◽  
Author(s):  
Stefan Galler ◽  
Oleg Andruchov ◽  
Gabriela M.M. Stephenson ◽  
D. George Stephenson

1987 ◽  
Vol 57 (4) ◽  
pp. 921-937 ◽  
Author(s):  
M. J. Gillespie ◽  
T. Gordon ◽  
P. R. Murphy

A reexamination of the question of specificity of reinnervation of fast and slow muscle was undertaken using the original "self" nerve supply to the fast lateral gastrocnemius (LG) and slow soleus muscles in the rat hindlimb. This paradigm takes advantage of the unusual situation of a common nerve branch, which supplies both a fast and slow muscle, and of the opportunity to keep the reinnervating nerve in its normal position. In addition it provides a test of the effects of cross-reinnervation among muscles of the same functional group. The properties of soleus and LG muscles and of individual muscle units were characterized in normal rats and in rats 4-14 mo after cutting the lateral gastrocnemius-soleus (LGS) nerve and suture of the proximal stump to the dorsal surface of the LG muscle. Individual muscle units were functionally isolated by stimulation of single motor axons to LG or soleus muscle contained in teased filaments in the L4 and L5 ventral roots. Motor units were classified as fast contracting fatiguable (FF), fast contracting fatigue resistant (FR), and slow (S) on the basis of criteria described in the cat by Burke et al. and applied to rat muscle units by Gillespie et al. Muscle fibers were classified as fast glycolytic (FG), fast oxidative glycolytic (FOG), and slow oxidative (SO) on the basis of histochemical staining for myosin ATPase, nicotinamide-adenine dinucleotide diaphorase (NADH-D), and alpha-glycerophosphate (alpha-GPD). Reinnervated muscles developed less force and weighed less in accordance with having fewer than normal motor units and having lost denervated muscle fibers. Normal LG contained a small proportion of S-type motor units (9%), whereas the majority (80%) of control soleus units were S type. After reinnervation, each muscle contained similar proportions of fast and slow motor units with S-type units constituting 30% of units in both muscles. When compared with the normal motor-unit sample, there was no significant change in average twitch and tetanic force in reinnervated muscles for each type of motor unit. However, the range within each type was greater, and there was considerable overlap between types. Twitch contraction time was inversely correlated with force in normal and reinnervated muscles as shown previously in self- and cross-reinnervated LGS in the cat. Changes in proportions of motor units in reinnervated LG were accompanied by corresponding changes in histochemical muscle types. This contrasted with reinnervated soleus in which the proportion of muscle fiber types was not significantly changed from normal despite significant change in motor-unit proportions.(ABSTRACT TRUNCATED AT 400 WORDS)


2019 ◽  
Author(s):  
Chloe A. Johnson ◽  
Jonathan Walklate ◽  
Marina Svicevic ◽  
Srboljub M. Mijailovich ◽  
Carlos Vera ◽  
...  

AbstractStriated muscle myosins are encoded by a large gene family in all mammals, including human. These isoforms define several of the key characteristics of the different striated muscle fiber types including maximum shortening velocity. We have previously used recombinant isoforms of the motor domains of eight different human myosin isoforms to define the actin.myosin cross-bridge cycle in solution. Here, we use a recently developed modeling approach MUSICO to explore how well the experimentally defined cross-bridge cycles for each isoform in solution can predict the characteristics of muscle fiber contraction including duty ratio, shortening velocity, ATP economy and the load dependence of these parameters. The work shows that the parameters of the cross-bridge cycle predict many of the major characteristics of each muscle fiber type and raises the question of what sequence changes are responsible for these characteristics.


2009 ◽  
Vol 57 (8) ◽  
pp. 787-800 ◽  
Author(s):  
Hannah S. Rhee ◽  
Catherine M. Steel ◽  
Frederik J. Derksen ◽  
N. Edward Robinson ◽  
Joseph F.Y. Hoh

We used immunohistochemistry to examine myosin heavy-chain (MyHC)-based fiber-type profiles of the right and left cricoarytenoideus dorsalis (CAD) and arytenoideus transversus (TrA) muscles of six horses without laryngoscopic evidence of recurrent laryngeal neuropathy (RLN). Results showed that CAD and TrA muscles have the same slow, 2a, and 2x fibers as equine limb muscles, but not the faster contracting fibers expressing extraocular and 2B MyHCs found in laryngeal muscles of small mammals. Muscles from three horses showed fiber-type grouping bilaterally in the TrA muscles, but only in the left CAD. Fiber-type grouping suggests that denervation and reinnervation of fibers had occurred, and that these horses had subclinical RLN. There was a virtual elimination of 2x fibers in these muscles, accompanied by a significant increase in the percentage of 2a and slow fibers, and hypertrophy of these fiber types. The results suggest that multiple pathophysiological mechanisms are at work in early RLN, including selective denervation and reinnervation of 2x muscle fibers, corruption of neural impulse traffic that regulates 2x and slow muscle fiber types, and compensatory hypertrophy of remaining fibers. We conclude that horses afflicted with mild RLN are able to remain subclinical by compensatory hypertrophy of surviving muscle fibers.


1974 ◽  
Vol 61 (2) ◽  
pp. 414-426 ◽  
Author(s):  
Robert S. Hikida ◽  
Joseph A. Lombardo

The pigeon's metapatagialis muscles, containing fast fibers in two slips and slow fibers in another slip, were excised for a third of their length, minced, and replaced into their previous sites. After regeneration, the pattern of fiber types and their ATPase and oxidative enzymes were examined histochemically. Ultrastructural examination was carried out on the fast fibers. After 4–17 wk the muscles had regenerated into patterns histochemically similar to the controls only within the slip containing fast fibers. The slow slip was much less regenerated, and had a histochemically embryonic composition. Fiber types were characterized and their cross-sectional areas measured, and the degree of atrophy was greatest in the large fast fibers and the slow fibers. Ultrastructural studies revealed a number of alterations of the mitochondria, including dense and light areas in the matrix and an altered pattern of the cristae into parallel tubular or vesicular aggregations. Other changes included dilated sarcoplasmic reticulum, myofibril disorganization, and a compaction of filaments. The slow fibers were thought to be slower in their regeneration rates because of the pattern of multiple innervation's producing a more complex regenerative pattern.


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