Hypertrophy and transcriptional regulation induced in myogenic cell line L6-C5 by an increase of extracellular calcium
Hypertrophy and transcriptional regulation induced in myogenic cell line L6-C5 by an increase of extracellular calcium
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DOI：
10.1002/jcp.20174
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发表时间：
2005-03-01
影响因子：
5.6
通讯作者：
Naro, F
中科院分区：
文献类型：
--
作者：
De Arcangelis, V;Coletti, D;Naro, F
Calcium plays a pivotal role in the establishment of the differentiated phenotype in myogenic cells but the involved molecular mechanisms are still matter of debate. Here we studied the effects of exposing L6-C5 myogenic cells to high extracellular Ca2+ concentration ([Ca2+](o)), which induces an increase of intracellular calcium ([Ca2+](i)) without involving Ca2+ release from the intracellular stores but exclusively due to plasma membrane influx (Naro et al., 2003). Exposure of L6-C5 cells to [Ca2+](o) up to 20 mM for 30 min, before shifting them into a differentiative medium, induced the appearance of multinucleated, myosin-positive myotubes, much larger than in control cells with an increased protein/DNA ratio. These large myotube showed nuclear accumulation of the hypertrophy marker GATA-2. The hypertrophic growth of these cells was blocked by cyclosporin A (CsA) FK506, or overexpression of a calcineurin-dominant negative protein, suggesting the involvement in this process of the Ca2+ responsive phosphatase calcineurin. Furthermore, transient exposure of L6-C5 cells to high [Ca2+](o) increased the expression of luciferase reporter driven by myoglobin (Mb) and beta-MHC promoters but not IIB-MHC and MCK promoters. Luciferase transcription driven by CK promoter was, instead, enhanced by mobilizing Ca2+ from the intracellular stores. These data indicate that a transient increase of [Ca2+](i) due to plasma-membrane influx is sufficient to induce a hypertrophic phenotype and an increased expression of slow-fiber genes but not fast-fiber genes. (C) 2004 Wiley-Liss, Inc.
