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The Journal of Histochemistry and... Feb 2020Histidine-rich glycoprotein (HRG) is a plasma protein synthesized by the liver. We have given the first evidence of a tissue localization of HRG demonstrating its...
Histidine-rich glycoprotein (HRG) is a plasma protein synthesized by the liver. We have given the first evidence of a tissue localization of HRG demonstrating its presence in skeletal muscle, associated with the zinc enzyme AMP deaminase (AMPD1). Moreover, we have shown that muscle cells do not synthesize HRG, but they can internalize it from plasma. We have recently demonstrated by confocal laser scanning microscopy that in human skeletal muscle, HRG is mainly localized in the myofibrils, preferentially at the I-band of the sarcomere, in the sarcoplasm, and in the nuclei. Using transmission electron microscopy and immunogold analysis, we carried out this study on human and rat normal skeletal muscles with the purpose to deepen the ultrastructural localization of HRG in skeletal muscle fibers. The immunogold analysis evidenced the presence of HRG in the sarcomeres, mainly in the I-band and to a less extent in the A-band, in the heterochromatin of nuclei, and in the sarcoplasmic reticulum. The colocalization of HRG and skeletal muscle AMPD1 was also analyzed. A colabeling of HRG and AMPD1 was evident at sarcomeric, sarcoplasmic reticulum, and nuclear levels. The significance of these interesting and new results is discussed in this article.
Topics: AMP Deaminase; Adult; Aged; Animals; Female; Humans; Intracellular Space; Male; Muscle Fibers, Skeletal; Protein Transport; Proteins; Rats
PubMed: 31880188
DOI: 10.1369/0022155419897573 -
Molecular Therapy : the Journal of the... Jul 2011
Topics: Clinical Trials, Phase II as Topic; Genetic Therapy; Heart Failure; Humans; Randomized Controlled Trials as Topic; Sarcoplasmic Reticulum Calcium-Transporting ATPases
PubMed: 21720375
DOI: 10.1038/mt.2011.123 -
Food Chemistry Mar 2022The subcellular distribution of calpain-1 and -2 and the proteolytical activity of myofibril-bound calpains in pork were investigated during 12 days cold storage. The...
The subcellular distribution of calpain-1 and -2 and the proteolytical activity of myofibril-bound calpains in pork were investigated during 12 days cold storage. The content of sarcoplasmic calpain-1 decreased during storage while myofibril-bound calpain-1 content first increased (P < 0.05) to 17% of that of 12 h-sarcoplasmic calpain-1 on day 6 followed by a gradual decrease with subsequent storage, suggesting that calpain-1 gradually translocated from sarcoplasm to myofibrils during the initial 6 days of postmortem storage. Intact desmin decreased (P < 0.05) after incubation of myofibrils with 0.05 mM Ca, and this was more pronounced with 5 mM Ca (P < 0.05). Ca titration curves of day 6 myofibrils showed two distinct proteolytic activities becoming activated in the range 0.03 to 0.06 mM and 0.4 to 0.8 mM Ca, respectively. The results suggest that both calpain-1 and calpain-2 binds to myofibrils during storage and subsequently degrade structural proteins including desmin.
Topics: Animals; Calpain; Desmin; Meat; Muscle, Skeletal; Myofibrils; Pork Meat; Postmortem Changes; Proteolysis; Red Meat; Swine
PubMed: 34818749
DOI: 10.1016/j.foodchem.2021.131347 -
The Journal of Biological Chemistry Mar 2018Naturally occurring mutations of a calcium ion transporter can cause a skin condition known as Darier's disease. In this issue of JBC, Mikkelsen describe a particularly...
Naturally occurring mutations of a calcium ion transporter can cause a skin condition known as Darier's disease. In this issue of JBC, Mikkelsen describe a particularly interesting Darier's mutation that alters calcium transport by disrupting a kinetic braking mechanism that is unique to the SERCA2b calcium pump isoform. The study provides new insight into the intrinsic regulation of this transporter and reveals how disruption of regulation can lead to disease in Darier's patients.
Topics: Calcium; Calcium Signaling; Darier Disease; Humans; Kinetics; Mutation; Protein Conformation; Sarcoplasmic Reticulum Calcium-Transporting ATPases
PubMed: 29667928
DOI: 10.1074/jbc.H118.002088 -
Cardiovascular Research May 2013
Topics: Animals; Heart Failure; Humans; Myocytes, Cardiac; Sarcoplasmic Reticulum
PubMed: 23504549
DOI: 10.1093/cvr/cvt058 -
Cell Calcium Dec 1988Under certain conditions of Ca2+ loading, cardiac myocytes, both isolated and in intact tissue, exhibit spontaneous, oscillatory Ca2+ transients due to Ca2+ release from... (Review)
Review
Under certain conditions of Ca2+ loading, cardiac myocytes, both isolated and in intact tissue, exhibit spontaneous, oscillatory Ca2+ transients due to Ca2+ release from the sarcoplasmic reticulum. These transients are not triggered by depolarization of the sarcolemma, though they themselves can generate depolarizing currents which can reach threshold to trigger an action potential. Spontaneous Ca2+ release occurs locally in a subcellular region and, once initiated, can propagate through the cell with a velocity of roughly 100 microns/s. Locally, the cytosolic Ca2+ concentration during spontaneous release is probably comparable to that during an electrically excited twitch. The mechanisms of initiation and propagation of spontaneous Ca2+ release are uncertain, but are probably closely related to the Ca2+-induced Ca2+ release which plays a role in normal excitation-contraction coupling. Spontaneous and triggered Ca2+ release appear to compete for a common pool of releasable sarcoplasmic reticulum Ca2+, with the result that spontaneous Ca2+ release imposes a beat-rate-dependent limit on the inotropic effect of interventions which increase intracellular Ca2+. Mathematical modeling of this effect shows that it can also explain increased diastolic tone, the development of aftercontractions and oscillatory restitution of contractility in states of 'Ca2+ overload'. Spontaneous Ca2+ release is a cause of arrhythmias, and may well play a role in some cases of systolic and diastolic myocardial dysfunction.
Topics: Animals; Calcium; Humans; Myocardium; Sarcoplasmic Reticulum
PubMed: 3066490
DOI: 10.1016/0143-4160(88)90005-x -
Structure (London, England : 1993) Mar 2022SERCA is a P-type ATPase embedded in the sarcoplasmic reticulum and plays a central role in muscle relaxation. SERCA's function is regulated by single-pass membrane...
SERCA is a P-type ATPase embedded in the sarcoplasmic reticulum and plays a central role in muscle relaxation. SERCA's function is regulated by single-pass membrane proteins called regulins. Unlike other regulins, dwarf open reading frame (DWORF) expressed in cardiac muscle has a unique activating effect. Here, we determine the structure and topology of DWORF in lipid bilayers using a combination of oriented sample solid-state NMR spectroscopy and replica-averaged orientationally restrained molecular dynamics. We found that DWORF's structural topology consists of a dynamic N-terminal domain, an amphipathic juxtamembrane helix that crosses the lipid groups at an angle of 64°, and a transmembrane C-terminal helix with an angle of 32°. A kink induced by Pro15, unique to DWORF, separates the two helical domains. A single Pro15Ala mutant significantly decreases the kink and eliminates DWORF's activating effect on SERCA. Overall, our findings directly link DWORF's structural topology to its activating effect on SERCA.
Topics: Calcium-Binding Proteins; Lipid Bilayers; Molecular Dynamics Simulation; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases
PubMed: 34875216
DOI: 10.1016/j.str.2021.11.003 -
Biochimica Et Biophysica Acta Jun 2009Ca2+-ATPase of muscle sarcoplasmic reticulum is an ATP-powered Ca2+-pump that establishes a >10,000 fold concentration gradient across the membrane. Its crystal... (Review)
Review
Ca2+-ATPase of muscle sarcoplasmic reticulum is an ATP-powered Ca2+-pump that establishes a >10,000 fold concentration gradient across the membrane. Its crystal structures have been determined for 9 different states that cover nearly the entire reaction cycle. Presented here is a brief structural account of the ion pumping process, with emphasis on why the structure has to be so.
Topics: Aspartic Acid; Binding Sites; Calcium; Cell Membrane; Models, Molecular; Protein Structure, Tertiary; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases
PubMed: 19010358
DOI: 10.1016/j.bbamcr.2008.10.008 -
European Journal of Translational... Apr 2020The functional state of RyR depends on the intracellular calcium concentration and on the oxidation state of its protein components in some particular sites and of some...
The functional state of RyR depends on the intracellular calcium concentration and on the oxidation state of its protein components in some particular sites and of some sentinel amino acids. In addition to the regulation of the RyR channel by exogenous substances (caffeine, ryanodine), ions environmental situations (oxidative state), other components, such as some endogenous proteins present in the sarcoplasm and/or in muscle membranes that are able to determine changes in Ca channel activity. Among these, calmodulin and S-100A could determine modifications in the status of RyR channel in the skeletal muscle. The currently available data can be justified the use of a simplified S-100/CaM and RyR interaction model for the regulation of Ca release in skeletal muscle. Under resting conditions, the CaM/S100A1 binding domain on RyR is predominantly dependent on S100A1. Vice versa when the intracellular Ca concentration becomes high as well as during repetitive (tetanus) stimulation, the Ca-CaM bond becomes dominant, shifting S100A1 from RyR and promoting channel inactivation. This may be one of the mechanism of muscle fatigue.
PubMed: 32499888
DOI: 10.4081/ejtm.2019.8839 -
American Journal of Physiology. Cell... May 2011
Calmodulin and S100A1 fine tune skeletal muscle E-C coupling. Focus on "Modulation of sarcoplasmic reticulum Ca2+ release in skeletal muscle expressing ryanodine receptor impaired in regulation by calmodulin and S100A1".
Topics: Animals; Calcium; Calmodulin; Excitation Contraction Coupling; Mice; Muscle, Skeletal; Ryanodine Receptor Calcium Release Channel; S100 Proteins; Sarcoplasmic Reticulum
PubMed: 21346150
DOI: 10.1152/ajpcell.00051.2011