The regulation of sarco(endo)plasmic reticulum calcium-ATPases (SERCA)

2015 ◽  
Vol 93 (10) ◽  
pp. 843-854 ◽  
Author(s):  
Andrew N. Stammers ◽  
Shanel E. Susser ◽  
Naomi C. Hamm ◽  
Michael W. Hlynsky ◽  
Dustin E. Kimber ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Tissue ◽  
Muscular Contraction ◽  
Regulatory Mechanisms ◽  
Post Translational Modifications ◽  
Disease States ◽  
Calcium Atpases ◽  
Plasmic Reticulum ◽  
Endogenous Proteins ◽  
Fast Twitch

The sarco(endo)plasmic reticulum calcium ATPase (SERCA) is responsible for transporting calcium (Ca2+) from the cytosol into the lumen of the sarcoplasmic reticulum (SR) following muscular contraction. The Ca2+ sequestering activity of SERCA facilitates muscular relaxation in both cardiac and skeletal muscle. There are more than 10 distinct isoforms of SERCA expressed in different tissues. SERCA2a is the primary isoform expressed in cardiac tissue, whereas SERCA1a is the predominant isoform expressed in fast-twitch skeletal muscle. The Ca2+ sequestering activity of SERCA is regulated at the level of protein content and is further modified by the endogenous proteins phospholamban (PLN) and sarcolipin (SLN). Additionally, several novel mechanisms, including post-translational modifications and microRNAs (miRNAs) are emerging as integral regulators of Ca2+ transport activity. These regulatory mechanisms are clinically relevant, as dysregulated SERCA function has been implicated in the pathology of several disease states, including heart failure. Currently, several clinical trials are underway that utilize novel therapeutic approaches to restore SERCA2a activity in humans. The purpose of this review is to examine the regulatory mechanisms of the SERCA pump, with a particular emphasis on the influence of exercise in preventing the pathological conditions associated with impaired SERCA function.

scholarly journals Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles

2016 ◽  
Vol 310 (8) ◽  
pp. C663-C672 ◽  
Author(s):  
Sébastien S. Dufresne ◽  
Nicolas A. Dumont ◽  
Antoine Boulanger-Piette ◽  
Val A. Fajardo ◽  
Daniel Gamu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Skeletal Muscle Function ◽  
Inotropic Effects ◽  
Plasmic Reticulum ◽  
Receptor Activator ◽  
Slow Twitch ◽  
And Function ◽  
Fast Twitch

Receptor-activator of nuclear factor-κB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscles preventing the loss of maximum specific force while promoting muscle atrophy, fatigability, and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 content, a Ca2+ sensor, and altered activity of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) modulating Ca2+ storage. Muscle RANK deletion had no significant effects on the sham or denervated slow-twitch soleus muscles. These data identify a novel role for RANK as a key regulator of Ca2+ storage and SERCA activity, ultimately affecting denervated skeletal muscle function.

scholarly journals Effect of glucocorticoid excess on skeletal muscle and heart protein synthesis in adult and old rats

1998 ◽  
Vol 79 (3) ◽  
pp. 297-304 ◽  
Author(s):  
Isabelle Savary ◽  
Elisabeth Debras ◽  
Dominique Dardevet ◽  
Claire Sornet ◽  
Pierre Capitan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Food Intake ◽  
Tibialis Anterior ◽  
Muscle Wasting ◽  
Recovery Period ◽  
Disease States ◽  
Old Rats ◽  
Fast Twitch

This study was carried out to analyse glucocorticoid-induced muscle wasting and subsequent recovery in adult (6-8 months) and old (18-24 months) rats because the increased incidence of various disease states results in hypersecretion of glucocorticoids in ageing. Adult and old rats received dexamethasone in their drinking water for 5 or 6 d and were then allowed to recover for 3 or 7 d. As dexamethasone decreased food intake, all groups were pair-fed to dexamethasonetreated old rats (i.e. the group that had the lowest food intake). At the end of the treatment, adult and old rats showed significant increases in blood glucose and plasma insulin concentrations. This increase disappeared during the recovery period. Protein synthesis of different muscles was assessed in vivo by a flooding dose of [13C]valine injected subcutaneously 50 min before slaughter. Dexamethasone induced a significant decrease in protein synthesis in fast-twitch glycolytic and oxidative glycolytic muscles (gastrocnemius, tibialis anterior, extensor digitorum longus). The treatment affected mostly ribosomal efficiency. Adult dexamethasone-treated rats showed an increase in protein synthesis compared with their pair-fed controls during the recovery period whereas old rats did not. Dexamethasone also significantly decreased protein synthesis in the predominantly oxidative soleus muscle but only in old rats, and increased protein synthesis in the heart of adult but not of old rats. Thus, in skeletal muscle, the catabolic effect of dexamethasone is maintained or amplified during ageing whereas the anabolic effect in heart is depressed. These results are consistent with muscle atrophy occurring with ageing.

The mutation of Pro789 to Leu reduces the activity of the fast-twitch skeletal muscle sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1) and is associated with Brody disease

2000 ◽  
Vol 106 (5) ◽  
pp. 482-491 ◽  
Author(s):  
Alex Odermatt ◽  
Kimby Barton ◽  
Vijay K. Khanna ◽  
Jean Mathieu ◽  
Diana Escolar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasmic Reticulum ◽  
Fast Twitch

scholarly journals Differential Association of Syntrophin Pairs with the Dystrophin Complex

1997 ◽  
Vol 138 (1) ◽  
pp. 81-93 ◽  
Author(s):  
Matthew F. Peters ◽  
Marvin E. Adams ◽  
Stanley C. Froehner
Keyword(s):  
Skeletal Muscle ◽  
Neuromuscular Junction ◽  
Regulatory Mechanisms ◽  
Signaling Proteins ◽  
Preferential Pairing ◽  
Associated Proteins ◽  
Fast Twitch Muscle ◽  
Fast Twitch ◽  
Oxide Synthase ◽  
Dystrophin Complex

The syntrophins are a multigene family of intracellular dystrophin-associated proteins comprising three isoforms, α1, β1, and β2. Based on their domain organization and association with neuronal nitric oxide synthase, syntrophins are thought to function as modular adapters that recruit signaling proteins to the membrane via association with the dystrophin complex. Using sequences derived from a new mouse β1-syntrophin cDNA, and previously isolated cDNAs for α1- and β2-syntrophins, we prepared isoform-specific antibodies to study the expression, skeletal muscle localization, and dystrophin family association of all three syntrophins. Most tissues express multiple syntrophin isoforms. In mouse gastrocnemius skeletal muscle, α1- and β1-syntrophin are concentrated at the neuromuscular junction but are also present on the extrasynaptic sarcolemma. β1-syntrophin is restricted to fast-twitch muscle fibers, the first fibers to degenerate in Duchenne muscular dystrophy. β2-syntrophin is largely restricted to the neuromuscular junction. The sarcolemmal distribution of α1- and β1-syntrophins suggests association with dystrophin and dystrobrevin, whereas all three syntrophins could potentially associate with utrophin at the neuromuscular junction. Utrophin complexes immunoisolated from skeletal muscle are highly enriched in β1- and β2-syntrophins, while dystrophin complexes contain mostly α1- and β1-syntrophins. Dystrobrevin complexes contain dystrophin and α1- and β1-syntrophins. From these results, we propose a model in which a dystrophin–dystrobrevin complex is associated with two syntrophins. Since individual syntrophins do not have intrinsic binding specificity for dystrophin, dystrobrevin, or utrophin, the observed preferential pairing of syntrophins must depend on extrinsic regulatory mechanisms.

Calcium uptake in mitochondria from different skeletal muscle types

1985 ◽  
Vol 59 (1) ◽  
pp. 137-141 ◽  
Author(s):  
W. L. Sembrowich ◽  
J. J. Quintinskie ◽  
G. Li
Keyword(s):  
Skeletal Muscle ◽  
Muscle Relaxation ◽  
Muscular Contraction ◽  
Slow Twitch Muscle ◽  
Fast Twitch Muscle ◽  
Uptake Process ◽  
Muscle Types ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Skeletal Muscle Types

The kinetics of calcium (Ca2+) uptake have been studied in mitochondria isolated from the different types of skeletal muscle. These studies demonstrate that the Ca2+ uptake properties of skeletal mitochondria are similar to those from liver and cardiac mitochondria. The Ca2+ carriers apparently have a high affinity for Ca2+ (Michaelis constants in the microM range). The relationship between Ca2+ uptake and initial Ca2+ concentration (10(-5) to 10(-7) M) is sigmoid in all mitochondria from the different skeletal muscle types suggesting that the uptake process is cooperative. Hill plots reveal coefficients of approximately 2 for mitochondria from fast-twitch muscle and 3.5 for slow-twitch muscle, adding further evidence to the concept that the uptake process is cooperative. An analysis of the potential role of mitochondria in the sequestration of Ca2+ during muscular contraction demonstrated that mitochondria from slow-twitch muscle of both rats and rabbits can potentially account for 100% of the relaxation rate at a low frequency of stimulation (5 Hz). In fast-twitch muscle, the mitochondria appear unable to play a significant role in muscle relaxation, particularly at stimulation frequencies that are considered in the normal physiological range. In summary, it appears that Ca2+ uptake by mitochondria from slow-twitch skeletal muscle has kinetic characteristics which make it important as a potential regulator of Ca2+ within the muscle cell under normal physiological conditions.

Acute exercise, epinephrine, and diabetes enhance insulin binding to skeletal muscle

1986 ◽  
Vol 250 (2) ◽  
pp. E186-E197
Author(s):  
B. A. Webster ◽  
S. R. Vigna ◽  
T. Paquette
Keyword(s):  
Skeletal Muscle ◽  
Acute Exercise ◽  
Binding Capacity ◽  
Insulin Binding ◽  
Muscular Contraction ◽  
Streptozotocin Induced Diabetes ◽  
Slow Twitch ◽  
Slow Twitch Fibers ◽  
Fast Twitch ◽  
Binding Curve

We measured insulin binding to crude membranes from rat skeletal muscle, with binding expressed relative to the sarcolemmal marker, cholesterol ester (CE). The amount of CE in the sarcolemma remained constant after streptozotocin-induced diabetes and acute exercise (swam for 90 min). Soleus (predominantly slow-twitch fibers) had higher insulin binding capacity than extensor digitorum longus (predominantly fast twitch). Both diabetes and acute exercise enhanced insulin binding. The shape of the enhanced insulin binding curve differed, however, between diabetes and acute exercise. Diabetes elicited a uniform increase in binding across the insulin concentrations measured (0.04-166 nM); acute exercise elicited the largest increase at the lower concentrations, suggesting different mechanisms cause the enhanced binding. Addition of 13.1 nM epinephrine to the perfusate in a rat hindlimb preparation increased insulin binding in a pattern similar to acute exercise. In contrast, muscular contraction stimulated by the sciatic nerve (1 Hz) or reduction of perfusate insulin from 100 to 40 pM, two additional correlates of acute exercise, had no effect. The increased insulin binding after acute exercise, therefore, appears to be mediated through elevated levels of catecholamines and not upregulation of the insulin receptor.

Melatonin: a novel strategy for prevention of obesity and fat accumulation in peripheral organs through the improvements of circadian rhythms and antioxidative capacity

2020 ◽  
Vol 3 (1) ◽  
pp. 58-76 ◽  
Author(s):  
Bohan Rong ◽  
Qiong Wu ◽  
Chao Sun
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Circadian Rhythms ◽  
Regulatory Mechanisms ◽  
Antioxidative Capacity ◽  
Unicellular Alga ◽  
Peripheral Tissues ◽  
Peripheral Organs ◽  
Regulatory Effects ◽  
Novel Strategy

Melatonin is a well-known molecule for its involvement in circadian rhythm regulation and its contribution to protection against oxidative stress in organisms including unicellular alga, animals and plants. Currently, the bio-regulatory effects of melatonin on the physiology of various peripheral tissues have drawn a great attention of scientists. Although melatonin was previously defined as a neurohormone secreted from pineal gland, recently it has been identified that virtually, every cell has the capacity to synthesize melatonin and the locally generated melatonin has multiple pathophysiological functions, including regulations of obesity and metabolic syndromes. Herein, we focus on the effects of melatonin on fat deposition in various peripheral organs/tissues. The two important regulatory mechanisms related to the topic, i.e., the improvements of circadian rhythms and antioxidative capacity will be thoroughly discussed since they are linked to several biomarkers involved in obesity and energy imbalance, including metabolism and immunity. Furthermore, several other functions of melatonin which may serve to prevent or promote obesity and energy dysmetabolism-induced pathological states are also addressed. The organs of special interest include liver, pancreas, skeletal muscle, adipose tissue and the gut microbiota.

scholarly journals Evidence for membrane microheterogeneity in the sarcoplasmic reticulum of fast twitch skeletal muscle.

1982 ◽  
Vol 257 (19) ◽  
pp. 11689-11695
Author(s):  
W B Van Winkle ◽  
R J Bick ◽  
D E Tucker ◽  
C A Tate ◽  
M L Entman
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Fast Twitch ◽  
Membrane Microheterogeneity
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