scholarly journals Intergenic bidirectional promoter and cooperative regulation of the IIx and IIb MHC genes in fast skeletal muscle

2008 ◽  
Vol 295 (1) ◽  
pp. R208-R218 ◽  
Author(s):  
Chiara Rinaldi ◽  
Fadia Haddad ◽  
Paul W. Bodell ◽  
Anqi X. Qin ◽  
Weihua Jiang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Antisense Rna ◽  
Bidirectional Promoter ◽  
Regulatory Elements ◽  
Feedback Mechanism ◽  
Medial Gastrocnemius ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Dynamic Regulation ◽  
Mhc Genes

This study investigated the dynamic regulation of IIx-IIb MHC genes in the fast white medial gastrocnemius (WMG) muscle in response to intermittent resistance exercise training (RE), a model associated with a rapid shift from IIb to IIx expression ( 11 ). We investigated the effect of 4 days of RE on the transcriptional activity across the skeletal MHC gene locus in the WMG in female Sprague-Dawley rats. Our results show that RE resulted in significant shifts from IIb to IIx observed at both the pre-mRNA and mRNA levels. An antisense RNA (xII NAT) was detected in the intergenic (IG) region between IIx and IIb, extending across the entire IIx gene and into its promoter. The expression of the xII NAT was positively correlated with IIb pre-mRNA ( R = +0.8), and negatively correlated with IIx pre-mRNA ( R = −0.8). Transcription mapping of the IIx–IIb IG region revealed the generation of sense IIb and xII NATs from a single promoter region. This bidirectional promoter is highly conserved among species and contains several regulatory elements that may be implicated in its regulation. These results suggest that the IIx and the IIb genes are physically and functionally linked via the bidirectional promoter. In order for the IIx MHC gene to be regulated, a feedback mechanism from the IG xII NAT is needed. In conclusion, the IG bidirectional promoter generating antisense RNA appears to be essential for the coordinated regulation of the skeletal muscle MHC genes during dynamic phenotype shifts.

scholarly journals Fast skeletal muscle-specific expression of a quail troponin I gene in transgenic mice.

1988 ◽  
Vol 8 (12) ◽  
pp. 5072-5079 ◽  
Author(s):  
P L Hallauer ◽  
K E Hastings ◽  
A C Peterson
Keyword(s):  
Skeletal Muscle ◽  
Transgenic Mice ◽  
Troponin I ◽  
Fiber Type ◽  
Regulatory Elements ◽  
Evolutionary Divergence ◽  
Mrna Levels ◽  
Fast Skeletal Muscle ◽  
Specific Expression ◽  
Exon 2

We have produced seven lines of transgenic mice carrying the quail gene encoding the fast skeletal muscle-specific isoform of troponin I (TnIf). The quail DNA included the entire TnIf gene, 530 base pairs of 5'-flanking DNA, and 1.5 kilobase pairs of 3'-flanking DNA. In all seven transgenic lines, normally initiated and processed quail TnIf mRNA was expressed in skeletal muscle, where it accumulated to levels comparable to that in quail muscle. Moreover, in the three lines tested, quail TnIf mRNA levels were manyfold higher in a fast skeletal muscle (gastrocnemius) than in a slow skeletal muscle (soleus). We conclude that the cellular mechanisms directing muscle fiber type-specific TnIf gene expression are mediated by cis-regulatory elements present on the introduced quail DNA fragment and that they control TnIf expression by affecting the accumulation of TnIf mRNA. These elements have been functionally conserved since the evolutionary divergence of birds and mammals, despite the major physiological and morphological differences existing between avian (tonic) and mammalian (twitch) slow muscles. In lines of transgenic mice carrying multiple tandemly repeated copies of the transgene, an aberrant quail TnIf transcript (differing from normal TnIf mRNA upstream of exon 2) also accumulated in certain tissues, particularly lung, brain, spleen, and heart tissues. However, this aberrant transcript was not detected in a transgenic line which carries only a single copy of the quail gene.

scholarly journals Regulation of an antisense RNA with the transition of neonatal to IIb myosin heavy chain during postnatal development and hypothyroidism in rat skeletal muscle

2012 ◽  
Vol 302 (7) ◽  
pp. R854-R867 ◽  
Author(s):  
Clay E. Pandorf ◽  
Weihua Jiang ◽  
Anqi X. Qin ◽  
Paul W. Bodell ◽  
Kenneth M. Baldwin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Postnatal Development ◽  
Heavy Chain ◽  
Antisense Rna ◽  
Transcriptional Repression ◽  
Mhc Genes ◽  
Regulatory Model ◽  
A Site ◽  
Comparative Phylogenetic Analysis

Postnatal development of fast skeletal muscle is characterized by a transition in expression of myosin heavy chain (MHC) isoforms, from primarily neonatal MHC at birth to primarily IIb MHC in adults, in a tightly coordinated manner. These isoforms are encoded by distinct genes, which are separated by ∼17 kb on rat chromosome 10. The neonatal-to-IIb MHC transition is inhibited by a hypothyroid state. We examined RNA products [mRNA, pre-mRNA, and natural antisense transcript (NAT)] of developmental and adult-expressed MHC genes (embryonic, neonatal, I, IIa, IIx, and IIb) at 2, 10, 20, and 40 days after birth in normal and thyroid-deficient rat neonates treated with propylthiouracil. We found that a long noncoding antisense-oriented RNA transcript, termed bII NAT, is transcribed from a site within the IIb-Neo intergenic region and across most of the IIb MHC gene. NATs have previously been shown to mediate transcriptional repression of sense-oriented counterparts. The bII NAT is transcriptionally regulated during postnatal development and in response to hypothyroidism. Evidence for a regulatory mechanism is suggested by an inverse relationship between IIb MHC and bII NAT in normal and hypothyroid-treated muscle. Neonatal MHC transcription is coordinately expressed with bII NAT. A comparative phylogenetic analysis also suggests that bII NAT-mediated regulation has been a conserved trait of placental mammals for most of the eutherian evolutionary history. The evidence in support of the regulatory model implicates long noncoding antisense RNA as a mechanism to coordinate the transition between neonatal and IIb MHC during postnatal development.

scholarly journals The Effects of Exogenous Lactate Administration on the IGF1/Akt/mTOR Pathway in Rat Skeletal Muscle

2020 ◽  
Vol 17 (21) ◽  
pp. 7805
Author(s):  
Sunghwan Kyun ◽  
Choongsung Yoo ◽  
Hun-Young Park ◽  
Jisu Kim ◽  
Kiwon Lim
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Expression ◽  
Lactate Concentration ◽  
Ring Finger ◽  
Receptor Protein ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Expression Levels ◽  
Igf Receptor

We investigated the effects of oral lactate administration on protein synthesis and degradation factors in rats over 2 h after intake. Seven-week-old male Sprague–Dawley rats were randomly divided into four groups (n = 8/group); their blood plasma levels of lactate, glucose, insulin, and insulin-like growth factor 1 (IGF1) were examined following sacrifice at 0, 30, 60, or 120 min after sodium lactate (2 g/kg) administration. We measured the mRNA expression levels of protein synthesis-related genes (IGF receptor, protein kinase B (Akt), mammalian target of rapamycin (mTOR)) or degradation-related genes (muscle RING-finger protein-1 (MuRF1), atrogin-1) and analyzed the protein expression and phosphorylation (activation) of Akt and mTOR. Post-administration, the plasma lactate concentration increased to 3.2 mmol/L after 60 min. Plasma glucose remained unchanged throughout, while insulin and IGF1 levels decreased after 30 min. The mRNA levels of IGF receptor and mTOR peaked after 60 min, and Akt expression was significantly upregulated from 30 to 120 min. However, MuRF1 and atrogin-1 expression levels were unaffected. Akt protein phosphorylation did not change significantly, whereas mTOR phosphorylation significantly increased after 30 min. Thus, lactate administration increased the mRNA and protein expression of protein-synthesis factors, suggesting that it can potentially promote skeletal muscle synthesis.

scholarly journals The Effect of TSH-Suppressive Dose of Levothyroxine On Skeletal Muscle In Ovariectomized Rats

2021 ◽  
Author(s):  
Jeong Hun Kim ◽  
Ji Min Kim ◽  
Byung-Joo Lee ◽  
In-Joo Kim ◽  
Kyoungjune Pak ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Nodular Goiter ◽  
Thyroid Stimulating Hormone ◽  
Ovariectomized Rats ◽  
Suppressive Therapy ◽  
Mrna Levels ◽  
Hormonal Changes ◽  
Sprague Dawley ◽  
Toxic Nodular Goiter

Abstract Hyperthyroidism is often observed in postmenopausal women due to conditions such as thyroiditis and toxic nodular goiter, Grave’s disease or thyroid stimulating hormone suppressive therapy for treating differentiated thyroid carcinoma (DTC). However, the effect of such hormonal changes on skeletal muscles in females remain unclear. Therefore, this study aimed to observe the effects of hyperthyroidism on the skeletal muscle of ovariectomized rats. We randomly divided female Sprague-Dawley rats into sham-operated (Sham), ovariectomized (OVX), and levothyroxine-treated ovariectomized groups (OVX+LT4). Levothyroxine was administered intraperitoneally at 0.3 mg/kg, daily for six weeks. Protein synthesis was increased after ovariectomy whereas protein synthesis was suppressed and protein degradation was increased in response to levothyroxine treatment. However, there was no difference in lean mass between the two groups. Collagen I levels were similar between the Sham and OVX groups, but were significantly decreased in the OVX+LT4 group. The mRNA levels of matrix metalloproteinase (MMP) ‐2 and ‐9 were similar between the Sham and OVX groups but were upregulated in the OVX+LT4 group. After ovariectomy, mitochondrial biogenesis and dynamics were changed; these changes were exacerbated in hyperthyroidism. Our findings indicate that in postmenopausal rats with hyperthyroidism, the progression of muscle weakness occurs through impaired regulation of signaling pathways related to extracellular matrix homeostasis, protein turnover, and mitochondrial quality.

Chronic β-blockade increases skeletal muscle β-adrenergicreceptor density and enhances contractile force

1997 ◽  
Vol 83 (2) ◽  
pp. 459-465 ◽  
Author(s):  
René J. L. Murphy ◽  
Phillip F. Gardiner ◽  
Guy Rousseau ◽  
Michel Bouvier ◽  
Louise Béliveau
Keyword(s):  
Skeletal Muscle ◽  
Adrenergic Receptor ◽  
Contractile Force ◽  
Medial Gastrocnemius ◽  
Receptor Density ◽  
Sprague Dawley ◽  
Oxidative Potential ◽  
Sprague Dawley Rats ◽  
Adrenergic Antagonist ◽  
Contractile Forces

Murphy, René J. L., Phillip F. Gardiner, Guy Rousseau, Michel Bouvier, and Louise Béliveau. Chronic β-blockade increases skeletal muscle β-adrenergic-receptor density and enhances contractile force. J. Appl. Physiol.83(2): 459–465, 1997.—The effects of a chronic 14-day administration of a selective β2-adrenergic-receptor antagonist (ICI-118551) on skeletal muscle were evaluated in female Sprague-Dawley rats. Chronic ICI-118551 treatment did not modify muscle mass, oxidative potential, or protein concentration of the medial gastrocnemius muscle, suggesting that maintenance of these skeletal muscle characteristics is not dependent on β2-adrenergic-receptor stimulation. However, the drug treatment increased β-adrenergic-receptor density of the lateral gastrocnemius (42%) and caused an increase in specific (g/g) isometric in situ contractile forces of the medial gastrocnemius [twitch, 56%; tetanic (200 Hz), 28%]. The elevated contractile forces observed after a chronic treatment with ICI-118551 were completely abolished when the β2-adrenergic antagonist was also administered acutely before measurement of contractile forces, suggesting that this response is β2-adrenergic-receptor dependent. Possible mechanisms for the increased forces were studied. Caffeine administration potentiated twitch forces but had little effect on tetanic force in control animals. Administration of dibutyryl adenosine 3′,5′-cyclic monophosphate in control animals also resulted in small increases of twitch force but did not modify tetanic forces. We conclude that increases in β-adrenergic-receptor density and the stimulation of the receptors by endogenous catecholamines appear to be responsible for increased contractile forces but that the mechanism remains to be demonstrated.

Myosin heavy chain mRNA transform to faster isoforms in immobilized skeletal muscle: a quantitative PCR study

1997 ◽  
Vol 82 (3) ◽  
pp. 977-982 ◽  
Author(s):  
Heidi Jänkälä ◽  
Veli-Pekka Harjola ◽  
Niels Erik Petersen ◽  
Matti Härkönen
Keyword(s):  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Quantitative Pcr ◽  
Heavy Chain ◽  
Quantitative Polymerase Chain Reaction ◽  
Type I ◽  
Mrna Levels ◽  
Total Rna ◽  
Mhc Genes ◽  
Pcr Method

Jänkälä, Heidi, Veli-Pekka Harjola, Niels Erik Petersen, and Matti Härkönen. Myosin heavy chain mRNA transform to faster isoforms in immobilized skeletal muscle: a quantitative PCR study. J. Appl. Physiol. 82(3): 977–982, 1997.—A quantitative polymerase chain reaction (PCR) method was used to measure the quantities of type I, IIa, IIx, and IIb myosin heavy chain (MHC) mRNA in total RNA preparations of the soleus, gastrocnemius, and plantaris muscles of normal and hindlimb-immobilized rats. Type IIx and even type IIb MHC mRNA were demonstrated at extremely low levels in normal soleus, 2.1 ± 0.4 × 105and 5.0 ± 0.2 × 105molecules of mRNA per microgram total RNA, respectively. Immobilization for 1 wk significantly altered the gene expression of MHC isoforms. In soleus, both type IIx and IIb MHC genes became significantly upregulated, 24-fold ( P < 0.005) and 2.6-fold ( P < 0.05), respectively. In gastrocnemius, the level of type IIa MHC mRNA decreased by 51% ( P < 0.01) and the level of type IIx MHC mRNA increased by 140% ( P < 0.05). In plantaris, the level of type IIa MHC mRNA decreased by 58% ( P < 0.005). In conclusion, immobilization changed the MHC mRNA profile in three different types of skeletal muscle toward faster isoforms. The quantitative results permit reliable evaluation of changes in mRNA levels.

A farnesyltransferase inhibitor attenuated β-adrenergic receptor downregulation in rat skeletal muscle

2002 ◽  
Vol 282 (1) ◽  
pp. R317-R322 ◽  
Author(s):  
Julie L. Lavoie ◽  
Angelino Calderone ◽  
Louise Béliveau
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Adrenergic Receptor ◽  
Cardiac Fibroblasts ◽  
Medial Gastrocnemius ◽  
Sprague Dawley ◽  
Farnesyltransferase Inhibitor ◽  
Concurrent Administration ◽  
Sprague Dawley Rats ◽  
Muscle Types

Farnesylation represents an essential posttranslational modification of several well-defined proteins implicated in the homologous desensitization of the β-adrenergic receptor (β-ADR). The following study examined the effect of a novel farnesyltransferase inhibitor, BMS-191563, on agonist-mediated β-ADR downregulation in skeletal muscle. Female Sprague-Dawley rats were treated for 12 days with the β2-adrenergic agonist clenbuterol (4 mg/kg) with or without the concurrent administration of BMS-191563 (2 mg · kg−1 · day−1). Clenbuterol promoted gastrocnemius muscle hypertrophy, whereas the soleus muscle was unaffected. Total β-ADR density was decreased by 45 and 40% in the soleus and medial gastrocnemius (MG), respectively, after clenbuterol treatment. BMS-191563 treatment did not prevent clenbuterol-stimulated MG hypertrophy, but markedly attenuated β-ADR downregulation in both muscle types. This latter effect in the soleus muscle was not associated with the inhibition of Ras farnesylation. Likewise, in rat cardiac fibroblasts, isoproterenol-mediated decrease of total β-ADR density was abrogated by the prior treatment with BMS-191563. Collectively, these data demonstrate that the mechanism(s) implicated in agonist-mediated β-ADR downregulation was sensitive to BMS-191563, thereby suggesting the involvement of farnesylated proteins.

scholarly journals Trafficking of dietary oleic, linolenic, and stearic acids in fasted or fed lean rats

2000 ◽  
Vol 278 (6) ◽  
pp. E1124-E1132 ◽  
Author(s):  
Daniel H. Bessesen ◽  
S. Holly Vensor ◽  
Matthew R. Jackman
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Stearic Acid ◽  
Dietary Fat ◽  
Medial Gastrocnemius ◽  
Sprague Dawley ◽  
Fed State ◽  
Liquid Meal ◽  
Fasted State ◽  
Sprague Dawley Rats

Increasing evidence supports the notion that there are significant differences in the health effects of diets enriched in saturated, as opposed to monounsaturated or polyunsaturated fat. However, the current understanding of how these types of fat differ in their handling by relevant tissues is incomplete. To examine the effects of fat type and nutritional status on the metabolic fate of dietary fat, we administered 14C-labeled oleic, linolenic, or stearic acid with a small liquid meal to male Sprague-Dawley rats previously fasted for 15 h (fasted) or previously fed ad libitum (fed).14CO2 production was measured for 8 h after tracer administration. The 14C content of gastrointestinal tract, serum, liver, skeletal muscle (soleus, lateral, and medial gastrocnemius), and adipose tissue (omental, retroperitoneal, and epididymal) was measured at six time points (2, 4, 8, 24, and 48 h and 10 days) after tracer administration. Plasma levels of glucose, insulin, and triglyceride were also measured. Oxidation of stearic acid was significantly less than that of either linolenic or oleic acid in both the fed and fasted states. This reduction was in part explained by a greater retention of stearic acid within skeletal muscle and liver. Oxidation of oleate and stearate were significantly lower in the fed state than in the fasted state. In the fasted state, liver and skeletal muscle were quantitatively more important than adipose tissue in the uptake of dietary fat tracers during the immediate postprandial period. In contrast, adipose tissue was quantitatively more important than skeletal muscle or liver in the fed state. The movement of carbons derived from dietary fat between tissues is a complex time-dependent process, which varies in response to the type of fat ingested and the metabolic state of the organism.

Short-term strength training and the expression of myostatin and IGF-I isoforms in rat muscle and tendon: differential effects of specific contraction types

2007 ◽  
Vol 102 (2) ◽  
pp. 573-581 ◽  
Author(s):  
K. M. Heinemeier ◽  
J. L. Olesen ◽  
P. Schjerling ◽  
F. Haddad ◽  
H. Langberg ◽  
...  
Keyword(s):  
Growth Factor ◽  
Medial Gastrocnemius ◽  
Mrna Levels ◽  
Eccentric Training ◽  
Sprague Dawley ◽  
Isometric Training ◽  
Specific Effects ◽  
Sprague Dawley Rats ◽  
Short Term Strength ◽  
Eccentric Actions

In skeletal muscle, an increased expression of insulin like growth factor-I isoforms IGF-IEa and mechano-growth factor (MGF) combined with downregulation of myostatin is thought to be essential for training-induced hypertrophy. However, the specific effects of different contraction types on regulation of these factors in muscle are still unclear, and in tendon the functions of myostatin, IGF-IEa, and MGF in relation to training are unknown. Female Sprague-Dawley rats were subjected to 4 days of concentric, eccentric, or isometric training ( n = 7–9 per group) of the medial gastrocnemius, by stimulation of the sciatic nerve during general anesthesia. mRNA levels for myostatin, IGF-IEa, and MGF in muscle and Achilles' tendon were measured by real-time RT-PCR. Muscle myostatin mRNA decreased in response to all types of training (2- to 8-fold) ( P < 0.05), but the effect of eccentric training was greater than concentric and isometric training ( P < 0.05). In tendon, myostatin mRNA was detected, but no changes were seen after exercise. IGF-IEa and MGF increased in muscle (up to 15-fold) and tendon (up to 4-fold) in response to training ( P < 0.01). In tendon no difference was seen between training types, but in muscle the effect of eccentric training was greater than concentric training for both IGF-IEa and MGF ( P < 0.05), and for IGF-IEa isometric training had greater effect than concentric ( P < 0.05). The results indicate a possible role for IGF-IEa and MGF in adaptation of tendon to training, and the combined changes in myostatin and IGF-IEa/MGF expression could explain the important effect of eccentric actions for muscle hypertrophy.

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