Annexin V, annexin VI, S100A1 and S100B in developing and adult avian skeletal muscles

Department of Experimental Medicine and Biochemical Sciences, Section of Anatomy, University of Perugia, Via del Giochetto, C.P. 81 Succ. 3, 06122 Perugia, Italy.
Neuroscience (Impact Factor: 3.36). 02/2002; 109(2):371-88. DOI: 10.1016/S0306-4522(01)00330-X
Source: PubMed


Annexins and S100 proteins constitute two multigenic families of Ca2+-modulated proteins that have been implicated in the regulation of both intracellular and extracellular activities. Some annexins can interact with certain S100 protein dimers thereby forming heterotetramers in which an S100 dimer crosslinks two copies of the partner annexin. It is suggested that S100 protein binding to an annexin might serve the function of regulating annexin function and annexin binding to an S100 protein might regulate S100 function. In the present study, annexin V, annexin VI (or ANXA5 and ANXA6, respectively, according to a novel nomenclature), S100A1 and S100B were analyzed for their subcellular localization in developing and adult avian skeletal muscles by confocal laser scanning microscopy, immunogold cytochemistry, and western blotting, and for their ability to form annexin–S100 heterocomplex in vivo by immunoprecipitation. These four proteins displayed distinct expression patterns, ANXA5 being the first to be expressed in myotubes (i.e. at embryonic day 8), followed by ANXA6 (at embryonic day 12) and S100A1 and S100B (between embryonic day 12 and embryonic day 15). The two annexins and the two S100 proteins were found associated to different extents with the sarcolemma, membranes of the sarcoplasmic reticulum, and putative transverse tubules where they appeared to be co-localized from embryonic day 18 onwards. No one of these proteins was found associated with the contractile apparatus of the sarcomeres. Immunoprecipitation studies indicated that ANXA6/S100A1 and ANXA6/S100B complexes formed in vivo. Whereas, ANXA5 was not recovered in S100A1 or S100B immunoprecipitates.

Full-text preview

Available from:
  • Source
    • "Furthermore, S100B protein is strategically located on the skeletal muscle membranes, sarcoplasmic reticulum, and transverse tubules acting in association with other proteins linked with calcium homeostasis (Arcuri et al. 2002). The demonstration that S100B is highly expressed and exerts functional properties in skeletal muscle provides the premise upon which to investigate S100B abnormalities in response to exercise-induced muscle damage (Arcuri et al. 2002; Donato et al. 2009; Tubaro et al. 2010; Riuzzi et al. 2011). Moreover, the assessments of serum concentrations of a candidate biomarker along with typical muscle biomarkers may help to determine the cell/tissue origin site and the behavior profile post-injury (Hasselblatt et al. 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to investigate the effect of running versus cycling exercises upon serum S100B levels and typical markers of skeletal muscle damage such as creatine kinase (CK), aspartate aminotransferase (AST) and myoglobin (Mb). Although recent work demonstrates that S100B is highly expressed and exerts functional properties in skeletal muscle, there is no previous study that tries to establish a relationship between muscle damage and serum S100B levels after exercise. We conducted a cross-sectional study on 13 male triathletes. They completed 2 submaximal exercise protocols at anaerobic threshold intensity. Running was performed on a treadmill with no inclination (RUN) and cycling (CYC) using a cycle-simulator. Three blood samples were taken before (PRE), immediately after (POST) and 1 h after exercise for CK, AST, Mb and S100B assessments. We found a significant increase in serum S100B levels and muscle damage markers in RUN POST compared with RUN PRE. Comparing groups, POST S100B, CK, AST and Mb serum levels were higher in RUN than CYC. Only in RUN, the area under the curve (AUC) of serum S100B is positively correlated with AUC of CK and Mb. Therefore, immediately after an intense exercise such as running, but not cycling, serum levels of S100B protein increase in parallel with levels of CK, AST and Mb. Additionally, the positive correlation between S100B and CK and Mb points to S100B as an acute biomarker of muscle damage after running exercise.
    Full-text · Article · Mar 2014 · Applied Physiology Nutrition and Metabolism
  • Source
    • "memb. Garbuglia et al. (2000), Arcuri et al. (2002) SR Díaz-Muñoz et al. (1990), Treves et al. (1997) RyR/L-type Prosser et al. (2008, 2010), Wright et al. (2008), Most et al. (2003) in neurons (SCG) Hernández-Ochoa et al. (2009) S100B K v /hEAG1 in rods Dopamine D2 Pozdnyakov et al. (1997), Rambotti et al. (1999), Duda et al. (2002), Sahoo et al. (2010), Neve et al. (2004) S100A10-annexin 2 Na v 1.8 K 2P /TASK in CFTR TRP 5, 6, ASC1a, 5-HT 1B van de Graaf et al. (2003), Okuse et al. (2002), Foulkes et al. (2006), Donier et al. (2005), Lotshaw (2007), Girard et al. (2002), Renigunta et al. (2006), Svenningsson et al. (2006) "
    [Show abstract] [Hide abstract]
    ABSTRACT: S100 Ca(2+)-binding proteins have been associated with a multitude of intracellular Ca(2+)-dependent functions including regulation of the cell cycle, cell differentiation, cell motility and apoptosis, modulation of membrane-cytoskeletal interactions, transduction of intracellular Ca(2+) signals, and in mediating learning and memory. S100 proteins are fine tuned to read the intracellular free Ca(2+) concentration and affect protein phosphorylation, which makes them candidates to modulate certain ion channels and neuronal electrical behavior. Certain S100s are secreted from cells and are found in extracellular fluids where they exert unique extracellular functions. In addition to their neurotrophic activity, some S100 proteins modulate neuronal electrical discharge activity and appear to act directly on ion channels. The first reports regarding these effects suggested S100-mediated alterations in Ca(2+) fluxes, K(+) currents, and neuronal discharge activity. Recent reports revealed direct and indirect interactions with Ca(2+), K(+), Cl(-), and ligand activated channels. This review focuses on studies of the physical and functional interactions of S100 proteins and ion channels.
    Full-text · Article · Apr 2012 · Frontiers in Pharmacology
  • Source
    • "The high level of S100B detected at day 1 post-injury likely reflected leakage of the protein from injured myofibers whereas the lower though relatively high levels found during the next 6 days might reflect ongoing clearance of leaked S100B and/or diminishing S100B leakage consequent to myofiber repair. Indeed, myofibers, quiescent satellite cells and proliferating myoblasts express S100B [7]–[9], and a subset of S100B+ lymphocytes [19] infiltrating the injured tissue might secrete the protein as well. By contrast, levels of bFGF amounted to ∼3 ng/muscle at day 1 post-injury, peaked (∼23 ng/muscle) at day 5 and declined to control levels between days 7 and 14 post-injury (Fig. 1A). "
    [Show abstract] [Hide abstract]
    ABSTRACT: In high-density myoblast cultures S100B enhances basic fibroblast growth factor (bFGF) receptor 1 (FGFR1) signaling via binding to bFGF and blocks its canonical receptor, receptor for advanced glycation end-products (RAGE), thereby stimulating proliferation and inhibiting differentiation. Here we show that upon skeletal muscle injury S100B is released from myofibers with maximum release at day 1 post-injury in coincidence with satellite cell activation and the beginning of the myoblast proliferation phase, and declining release thereafter in coincidence with reduced myoblast proliferation and enhanced differentiation. By contrast, levels of released bFGF are remarkably low at day 1 post-injury, peak around day 5 and decline thereafter. We also show that in low-density myoblast cultures S100B binds RAGE, but not bFGF/FGFR1 thereby simultaneously stimulating proliferation via ERK1/2 and activating the myogenic program via p38 MAPK. Clearance of S100B after a 24-h treatment of low-density myoblasts results in enhanced myotube formation compared with controls as a result of increased cell numbers and activated myogenic program, whereas chronic treatment with S100B results in stimulation of proliferation and inhibition of differentiation due to a switch of the initial low-density culture to a high-density culture. However, at relatively high doses, S100B stimulates the mitogenic bFGF/FGFR1 signaling in low-density myoblasts, provided bFGF is present. We propose that S100B is a danger signal released from injured muscles that participates in skeletal muscle regeneration by activating the promyogenic RAGE or the mitogenic bFGF/FGFR1 depending on its own concentration, the absence or presence of bFGF, and myoblast density.
    Full-text · Article · Jan 2012 · PLoS ONE
Show more