5.3.2. Insulin-like growth factor s

5.3.2. Insulin-like growth factor signaling in fish skeletal muscle
Different studies have shown the signaling molecules activated by IGFs and their involvement in fish muscle growth. Particularly, IGF1 activates the MAPK/ERK and PI3K/AKT signaling pathways in fish skeletal muscle in vivo and in vitro in different fish species(Fig. 3), including the fine flounder, rainbow trout, and gilthead sea bream (Castillo et al., 2006; Codina et al., 2008; Fuentes et al., 2011; Montserrat et al., 2007, 2012). IGF2 also activates these pathways in the myogenic cells of gilthead sea bream and rainbow trout (Codina et al., 2008; Montserrat et al., 2012) (Fig. 3). Interestingly, in gilthead sea bream myocytes, IGF2 activates the MAPK/ ERK and PI3K/AKT pathways stronger than IGF1 (Montserrat et al., 2012), suggesting that IGF2 is more potent than IGF1 in stimulating muscle growth in this species (Rius-Francino et al., 2011). Conversely, in myogenic cells of rainbow trout, IGF1 and IGF2 have the same effects and activate both signaling pathways (Codina et al., 2008). Using the same model incubations with PD98059 or wortmanin decrease IGF1-stimulated activation of the MAPK/ERK and PI3K/AKT pathways, respectively (Castillo et al., 2006; Montserrat et al., 2012). Moreover, treatments with wortmanin also decrease IGF1-stimulated MAPK/ERK activation (Castillo et al., 2006), suggesting a cross-talk between both signaling pathways, probably via Ras protein as in mammals (Katz and McCormick, 1997). Incubation
with these inhibitors decreases IGF1-stimulated glucose uptake in myogenic cells of rainbow trout and gilthead sea bream (Castillo et al., 2004; Codina et al., 2008; Montserrat et al., 2012). Using myogenic cells of rainbow trout, treatments with rapamycin decrease the phosphorylation of P70S6K and 4EBP1, whereas treatment with either amino acids or insulin leads to an increased activation of these molecules (Seiliez et al., 2008).
In fish, IGF1 is the main regulator of muscle growth, and the signaling pathways involved in this process have recently been identified. Macqueen et al. (2011) reported differential expression of tor and 4ebp1 in muscle of different Arctic charr populations. In particular, Arctic charr dwarf morphs have less basal mRNA contents of
tor and 4ebp1 in muscle than in populations with a larger phenotype (Macqueen et al., 2011). These results provide direct evidence for suggesting that signaling molecules such as TOR and 4EBP1 are directly regulating muscle growth in teleosts. Further evidence hasbeen provided using the fine flounder as model. In this species, was recently suggested that TOR is the main regulator of muscle growth and metabolism, integrating different inputs such as growth factors (e.g IGF1), nutrients (e.g. amino acids), and energy status(e.g. [AMP:ATP] via AMPK) (Fuentes et al., 2013). Also, in the fine flounder in vivo blocking of Mek1 with PD98059 and TOR using rapamycin during refeeding after 3 weeks of fasting inactivates ERK and P70S6 K-4EBP1, respectively (E.N. Fuentes, I.E. Einarsdottir, A. Molina and B.Th. Björnsson, unpublished data). The inactivation of both signaling pathways differentially affects muscle cellularity, growth performance, and growth-related genes. Treatments with PD98058 particularly have more attenuated effects onmuscle growth in comparison with treatments with rapamycin. Blocking Mek1 leads to a diminished muscle hypertrophy, due to a low expression of muscle- derived igf1. On the other hand, treatments with rapamycin trigger muscle wasting in the fine flounder, abolishing muscle hypertrophy through the downregulation of igf1, igf2, igfbp4, and igfbp5 concomitant with the upregulation of igfbp2, igfbp3, atrogin1, and murf1 (E.N. Fuentes, I.E. Einarsdottir, A.Molina and B.Th. Björnsson,
unpublished data). These results highlight the fact that the MAPK/ERK and TOR/P70S6K-4EBP1 pathways not only regulate processes such as proliferation and protein synthesis, but also affect the expression of important growth-related genes (Fig. 3).
Previously, was exposed the role of IGF1 as a key molecule preventing muscle atrophy in fish and recent research has started to identified the signaling pathways involved in this process (Fig. 3). In rainbow trout skeletal muscle, IGF1 activates AKT and subsequently inactivates FOXO transcription factors via phosphorylation (Cleveland and Weber, 2010; Fuentes et al., 2011, 2012b; Seiliez et al., 2010, 2011), thus preventing its nuclear translocation in a time-dependent manner (Seiliez et al., 2011). Using the same model, IGF1 also prevents the activation of the ubiquitin-proteasome pathways, decreasing protein degradation (Cleveland and Weber,2010).

ผลลัพธ์ (ไทย) 1:

5.3.2. Insulin-like growth factor signaling in fish skeletal muscleDifferent studies have shown the signaling molecules activated by IGFs and their involvement in fish muscle growth. Particularly, IGF1 activates the MAPK/ERK and PI3K/AKT signaling pathways in fish skeletal muscle in vivo and in vitro in different fish species(Fig. 3), including the fine flounder, rainbow trout, and gilthead sea bream (Castillo et al., 2006; Codina et al., 2008; Fuentes et al., 2011; Montserrat et al., 2007, 2012). IGF2 also activates these pathways in the myogenic cells of gilthead sea bream and rainbow trout (Codina et al., 2008; Montserrat et al., 2012) (Fig. 3). Interestingly, in gilthead sea bream myocytes, IGF2 activates the MAPK/ ERK and PI3K/AKT pathways stronger than IGF1 (Montserrat et al., 2012), suggesting that IGF2 is more potent than IGF1 in stimulating muscle growth in this species (Rius-Francino et al., 2011). Conversely, in myogenic cells of rainbow trout, IGF1 and IGF2 have the same effects and activate both signaling pathways (Codina et al., 2008). Using the same model incubations with PD98059 or wortmanin decrease IGF1-stimulated activation of the MAPK/ERK and PI3K/AKT pathways, respectively (Castillo et al., 2006; Montserrat et al., 2012). Moreover, treatments with wortmanin also decrease IGF1-stimulated MAPK/ERK activation (Castillo et al., 2006), suggesting a cross-talk between both signaling pathways, probably via Ras protein as in mammals (Katz and McCormick, 1997). Incubationมีสารยับยั้งเหล่านี้ลดการดูดซึมกลูโคสที่ถูกกระตุ้น IGF1 ในเซลล์ myogenic ปลาเทราต์สายรุ้งและไท gilthead (Castillo et al. 2004 Codina et al. 2008 มอนต์เซอร์รัต et al. 2012) ใช้เซลล์ myogenic ของปลาเทราต์สายรุ้ง รักษา ด้วย rapamycin ลด phosphorylation ของ P70S6K และ 4EBP1 ในขณะที่การรักษา ด้วยกรดอะมิโนหรืออินซูลินที่นำไปสู่การเปิดใช้งานที่เพิ่มขึ้นของโมเลกุลเหล่านี้ (Seiliez et al. 2008)ในปลา IGF1 เป็นหลักควบคุมการเจริญเติบโตของกล้ามเนื้อ และล่าสุดมีการระบุเส้นทางส่งสัญญาณที่เกี่ยวข้องในกระบวนการนี้ Macqueen et al. (2011) รายงานการแสดงทอร์และ 4ebp1 ในกล้ามเนื้อของประชากรผับอาร์กติกแตกต่างแตกต่าง โดยเฉพาะอย่างยิ่ง เปลี่ยนรูปร่างแคระผับอาร์กติกมีน้อยหา mRNA แรกเริ่มของtor and 4ebp1 in muscle than in populations with a larger phenotype (Macqueen et al., 2011). These results provide direct evidence for suggesting that signaling molecules such as TOR and 4EBP1 are directly regulating muscle growth in teleosts. Further evidence hasbeen provided using the fine flounder as model. In this species, was recently suggested that TOR is the main regulator of muscle growth and metabolism, integrating different inputs such as growth factors (e.g IGF1), nutrients (e.g. amino acids), and energy status(e.g. [AMP:ATP] via AMPK) (Fuentes et al., 2013). Also, in the fine flounder in vivo blocking of Mek1 with PD98059 and TOR using rapamycin during refeeding after 3 weeks of fasting inactivates ERK and P70S6 K-4EBP1, respectively (E.N. Fuentes, I.E. Einarsdottir, A. Molina and B.Th. Björnsson, unpublished data). The inactivation of both signaling pathways differentially affects muscle cellularity, growth performance, and growth-related genes. Treatments with PD98058 particularly have more attenuated effects onmuscle growth in comparison with treatments with rapamycin. Blocking Mek1 leads to a diminished muscle hypertrophy, due to a low expression of muscle- derived igf1. On the other hand, treatments with rapamycin trigger muscle wasting in the fine flounder, abolishing muscle hypertrophy through the downregulation of igf1, igf2, igfbp4, and igfbp5 concomitant with the upregulation of igfbp2, igfbp3, atrogin1, and murf1 (E.N. Fuentes, I.E. Einarsdottir, A.Molina and B.Th. Björnsson,unpublished data). These results highlight the fact that the MAPK/ERK and TOR/P70S6K-4EBP1 pathways not only regulate processes such as proliferation and protein synthesis, but also affect the expression of important growth-related genes (Fig. 3).Previously, was exposed the role of IGF1 as a key molecule preventing muscle atrophy in fish and recent research has started to identified the signaling pathways involved in this process (Fig. 3). In rainbow trout skeletal muscle, IGF1 activates AKT and subsequently inactivates FOXO transcription factors via phosphorylation (Cleveland and Weber, 2010; Fuentes et al., 2011, 2012b; Seiliez et al., 2010, 2011), thus preventing its nuclear translocation in a time-dependent manner (Seiliez et al., 2011). Using the same model, IGF1 also prevents the activation of the ubiquitin-proteasome pathways, decreasing protein degradation (Cleveland and Weber,2010).