S100B causes apoptosis in a myoblast cell line in a RAGE-independent manner.
S100B, a Ca(2+)-modulated protein with both intracellular and extracellular regulatory roles, is most abundant in astrocytes, is expressed in various amounts in several non-nervous cells and is also found in normal serum. Astrocytes secrete S100B, and extracellular S100B exerts trophic and toxic effects on neurons depending on its concentration, in part by interacting with the receptor for advanced glycation end products (RAGE). The presence of S100B in normal serum and elevation of its serum concentration in several non-nervous pathological conditions suggest that S100B-expressing cells outside the brain might release the protein and S100B might affect non-nervous cells. Recently we reported that at picomolar to nanomolar doses S100B inhibits rat L6 myoblast differentiation via inactivation of p38 kinase in a RAGE-independent manner. We show here that at >or=5 nM in the absence of and at >100 nM in the presence of serum S100B causes myoblast apoptosis via stimulation of reactive oxygen species (ROS) production and inhibition of the pro-survival kinase, extracellular signal-regulated kinase (ERK)1/2, again in a RAGE-independent manner. Together with our previous data, the present results suggest that S100B might participate in the regulation of muscle development and regeneration by two independent mechanism, i.e., by inhibiting crucial steps of the myogenic program at the physiological levels found in serum and by causing elevation of ROS production and myoblast apoptosis following accumulation in serum and/or muscle extracellular space. Our data also suggest that RAGE has no role in the transduction of S100B effects on myoblasts, implying that S100B can interact with more than one receptor to affect its target cells.
Sorci
Guglielmo
G
Department of Experimental Medicine and Biochemical Sciences, Section of Anatomy, University of Perugia, Perugia, Italy.
Riuzzi
Francesca
F
Agneletti
Anna Lisa
AL
Marchetti
Cristina
C
Donato
Rosario
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D017127:Glycation End Products, Advanced; D007150:Immunohistochemistry; D032446:Myoblasts / Q000187:drug effects* / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000494:pharmacology*; D014162:Transfection
D017127:Glycation End Products, Advanced; D009414:Nerve Growth Factors; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat