Showing papers by "Rosario Donato published in 2013"

S100B protein in tissue development, repair and regeneration

Abstract: The Ca2+-binding protein of the EF-hand type, S100B, exerts both intracellular and extracellular regulatory activities. As an intracellular regulator, S100B is involved in the regulation of energy metabolism, transcription, protein phosphorylation, cell proliferation, survival, differentiation and motility, and Ca2+ homeostasis, by interacting with a wide array of proteins (i.e., enzymes, enzyme substrates, cytoskeletal subunits, scaffold/adaptor proteins, transcription factors, ubiquitin E3 ligases, ion channels) in a restricted number of cell types. As an extracellular signal, S100B engages the pattern recognition receptor, receptor for advanced glycation end-products (RAGE), on immune cells as well as on neuronal, astrocytic and microglial cells, vascular smooth muscle cells, skeletal myoblasts and cardiomyocytes. However, RAGE may not be the sole receptor activated by S100B, the protein being able to enhance bFGF-FGFR1 signaling by interacting with FGFR1-bound bFGF in particular cell types. Moreover, extracellular effects of S100B vary depending on its local concentration. Increasing evidence suggests that at the concentration found in extracellular fluids in normal physiological conditions and locally upon acute tissue injury, which is up to a few nM levels, S100B exerts trophic effects in the central and peripheral nervous system and in skeletal muscle tissue thus participating in tissue homeostasis. The present commentary summarizes results implicating intracellular and extracellular S100B in tissue development, repair and regeneration.

HuR and miR-1192 regulate myogenesis by modulating the translation of HMGB1 mRNA.

Abstract: The nuclear protein HMGB1 is involved in muscle fibre formation. Here, Dormoy-Raclet et al. show that during muscle cell differentiation, the RNA-binding protein HuR promotes HMGB1 mRNA translation by preventing its repression by miR-1192.

Hypoxia Promotes Danger-mediated Inflammation via Receptor for Advanced Glycation End Products in Cystic Fibrosis

Abstract: Rationale: Hypoxia regulates the inflammatory-antiinflammatory balance by the receptor for advanced glycation end products (RAGE), a versatile sensor of damage-associated molecular patterns. The multiligand nature of RAGE places this receptor in the midst of chronic inflammatory diseases.Objectives: To characterize the impact of the hypoxia-RAGE pathway on pathogenic airway inflammation preventing effective pathogen clearance in cystic fibrosis (CF) and elucidate the potential role of this danger signal in pathogenesis and therapy of lung inflammation.Methods: We used in vivo and in vitro models to study the impact of hypoxia on RAGE expression and activity in human and murine CF, the nature of the RAGE ligand, and the impact of RAGE on lung inflammation and antimicrobial resistance in fungal and bacterial pneumonia.Measurements and Main Results: Sustained expression of RAGE and its ligand S100B was observed in murine lung and human epithelial cells and exerted a proximal role in promoting inflammation in...

Causes of elevated serum levels of S100B protein in athletes.

Abstract: In a recent report, Schulte et al. (2012) have measured elevated serum levels of S100B protein in athletes in the absence of traumatic brain injury (TBI) of which high serum S100B is one accepted biomarker. The authors have hypothesized that such an increase may be consequent to tissue hypoperfusion reflected by blood lactate concentrations and/or increased serotonin activity reflected by prolactin levels. However, sodium lactate infusion into human subjects resulted in no changes in serum S100B, and enhanced prolactin levels were also excluded as a cause of increased serum S100B after physical activity (Schulte et al. 2012). Thus, the authors concluded that neither increased blood lactate nor serum prolactin plays an exclusive role in the regulation of S100B. Also, the cause of elevated serum S100B in athletes has remained unidentified. It is known that serum levels of S100B increase remarkably following an intense physical exercise, and that intense physical exercise is associated with reversible skeletal muscle tissue damage and release of intracellular proteins. There is evidence that upon acute muscle injury S100B, that is expressed in mature muscle myofibers, is rapidly and massively released from injured muscle tissue (Riuzzi et al. 2012 and references therein), in advance of other factors such as bFGF and HMGB1 (amphoterin) shown to regulate myogenesis. The local concentration of released S100B may thus be as high (although in the subnanomolar-nanomolar range) as to regulate myoblast proliferation and differentiation (Riuzzi et al. 2012), which raises the possibility that the protein may participate in the process of skeletal muscle regeneration (Fig. 1a). In accordance with this possibility, current work indicates that blockade of S100B released from skeletal myofibers upon acute injury results in significantly delayed muscle regeneration (F. Riuzzi, G. Sorci, S. Beccafico and R. Donato, manuscript in preparation). Clearly, S100B released from damaged myofibers can diffuse into the bloodstream (Fig. 1a), also as suggested by the kinetics of its local decline after day 1 post-injury (Riuzzi et al. 2012), thus explaining its enhanced serum levels after intense physical exercise. Another potential cause of increased serum S100B is catecholamine-dependent activation of adipocytes that occurs during intense physical exercise. It is known that S100B is released by catecholamine-treated adipocytes along with free fatty acids that can diffuse into the bloodstream (Fig. 1b). In conclusion, the rise in serum S100B in coincidence with an intense physical activity (in the absence of TBI) may well depend on reversible skeletal muscle tissue damage and enhanced release from adipocytes. In this respect, it should be kept in mind that S100B is expressed in great abundance by astrocytes, oligodendrocytes and ependymocytes in the central nervous system, by Schwann cells and ganglion glial cells in the peripheral nervous system as well as by several non-nervous cells including adipocytes. Considering the high abundance of skeletal muscle and adipose tissue, it is conceivable that rises in Communicated by Håkan Westerblad.