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The insulin-like growth factor-I (IGF-I) is a key regulator of skeletal muscle growth in vertebrates, promoting mitogenic and anabolic effects through the activation of the MAPK/ERK and the PI3K/Akt signaling pathways. Nutrition also affects skeletal muscle growth, activating intracellular pathways and inducing protein synthesis and accretion. Thus, both hormonal and nutritional signaling regulate muscle mass. In this context, plasma IGF-I levels and the activation of both pathways in response to food were evaluated in the fine flounder using fasting and refeeding trials. The present study describes for the first time in a nonmammalian species that the MAPK/ERK and PI3K/Akt are activated by exogenous circulating IGF-I, as well as showing that the MAPK/ERK pathway activation is modulated by the nutritional status. Also, these results show that there is a time-dependent regulation of IGF-I plasma levels and its signaling pathways in muscle. Together, these results suggest that the nutritionally managed IGF-I could be regulating the activation of the MAPK/ERK and the PI3K/Akt signaling pathways differentially according to the nutritional status, triggering different effects in growth parameters and therefore contributing to somatic growth in fish. This study contributes to the understanding of the nutrient regulation of IGF-I and its signaling pathways in skeletal muscle growth in nonmammalian species, therefore providing insight concerning the events controlling somatic growth in vertebrates.

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ϩ or repetitive extracellular field potential pulses induces calcium release from internal stores. The two components of this release are mediated by either ryanodine receptors or inositol 1,4,5-trisphosphate (IP3) receptors and show differences in kinetics, amplitude, and subcellular localization. We have reported that the transcriptional regulators including ERKs, cAMP/Ca 2ϩ -response element binding protein, c-fos, c-jun, and egr-1 are activated by K ϩ -induced depolarization and that their activation requires IP 3-dependent calcium release. We presently describe the activation of the nuclear transcription factor NF-B in response to depolarization by either high K ϩ (chronic) or electrical pulses (fluctuating). Calcium transients of relative short duration activate an NF-B reporter gene to an intermediate level, whereas long-lasting calcium increases obtained by prolonged electrical stimulation protocols of various frequencies induce maximal activation of NF-B. This activation is independent of extracellular calcium, whereas calcium release mediated by either ryanodine or IP3 receptors contribute in all conditions tested. NF-B activation is mediated by IB␣ degradation and p65 translocation to the nucleus. Partial blockade by N-acetyl-L-cysteine, a general antioxidant, suggests the participation of reactive oxygen species. Calcium-dependent signaling pathways such as those linked to calcineurin and PKC also contribute to NF-B activation by depolarization, as assessed by blockade through pharmacological agents. These results suggest that NF-B activation in skeletal muscle cells is linked to membrane depolarization and depends on the duration of elevated intracellular calcium. It can be regulated by sequential activation of calcium release mediated by the ryanodine and by IP3 receptors. electrical stimulation; transcription; intracellular calcium stores CALCIUM IONS PLAY a central role in transcriptional regulation (7,12,15,22,45). The calcium-related transcription factors involve cytoplasmic and/or nuclear signaling pathways (19,22,52). In addition, nuclear calcium increase can directly modify transcription factors or modulate the chromatin structure as well as other elements that play a role in the regulation of the general transcription machinery (44). Transcriptional responses will depend on the particular nature of the stimulusinduced calcium transients, which may vary in their amplitude, kinetics, and spatial properties (17, 20 -22, 26).Skeletal muscle cells provide a unique environment where regulation of transcription must occur within a background of strong oscillatory calcium levels. Our laboratory has reported the presence of a complex pattern of calcium increase induced by depolarization, related to excitation-contraction and to excitation-transcription signaling in cultured muscle cells. In addition to the fast calcium transient mediated by the ryanodine receptor (RyR) channels, which drives muscle contraction, there is an inositol 1,4,5-trisphosphate (IP 3 ) receptor (IP 3 R)-mediated calcium relea...

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