Sorci Guglielmo, Riuzzi Francesca, Agneletti Anna Lisa, Marchetti Cristina, Donato Rosario
Section of Anatomy, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06122 Perugia, Italy.
Mol Cell Biol. 2003 Jul;23(14):4870-81. doi: 10.1128/MCB.23.14.4870-4881.2003.
S100B is a Ca(2+)-modulated protein of the EF-hand type with both intracellular and extracellular roles. S100B, which is most abundant in the brain, has been shown to exert trophic and toxic effects on neurons depending on the concentration attained in the extracellular space. S100B is also found in normal serum, and its serum concentration increases in several nervous and nonnervous pathological conditions, suggesting that S100B-expressing cells outside the brain might release the protein and S100B might exert effects on nonnervous cells. We show here that at picomolar to nanomolar levels, S100B inhibits myogenic differentiation of rat L6 myoblasts via inactivation of p38 kinase with resulting decrease in the expression of the myogenic differentiation markers, myogenin, muscle creatine kinase, and myosin heavy chain, and reduction of myotube formation. Although myoblasts express the multiligand receptor RAGE, which has been shown to transduce S100B effects on neurons, S100B produces identical effects on myoblasts overexpressing either full-length RAGE or RAGE lacking the transducing domain. This suggests that S100B affects myoblasts by interacting with another receptor and that RAGE is not the only receptor for S100B. Our data suggest that S100B might participate in the regulation of muscle development and regeneration by inhibiting crucial steps of the myogenic program in a RAGE-independent manner.
S100B是一种EF手型的Ca(2+)调节蛋白，在细胞内和细胞外均发挥作用。S100B在大脑中含量最为丰富，已证明其根据细胞外空间中达到的浓度对神经元产生营养和毒性作用。在正常血清中也可检测到S100B，在几种神经和非神经病理状态下其血清浓度会升高，这表明大脑外表达S100B的细胞可能会释放该蛋白，且S100B可能对非神经细胞产生影响。我们在此表明，在皮摩尔至纳摩尔水平，S100B通过使p38激酶失活来抑制大鼠L6成肌细胞的肌源性分化，导致肌源性分化标志物肌细胞生成素、肌肉肌酸激酶和肌球蛋白重链的表达降低，以及肌管形成减少。虽然成肌细胞表达多配体受体RAGE，该受体已被证明可转导S100B对神经元的作用，但S100B对过表达全长RAGE或缺乏转导结构域的RAGE的成肌细胞产生相同的作用。这表明S100B通过与另一种受体相互作用来影响成肌细胞，且RAGE不是S100B的唯一受体。我们的数据表明，S100B可能通过以RAGE非依赖的方式抑制肌源性程序的关键步骤来参与肌肉发育和再生的调节。
