Bacterial lipopolysaccharide induces rainbow trout myotube atrophy via Akt/FoxO1/Atrogin-1 signaling pathway  

作　　者：J.E. Aedo A.E. Reyes R. Avendano-Herrera A. Molina J.A. Valdesl 

机构地区：[1]Facultad de Ciencias Biologicas, Universidad AndrOs Bello, Santiago 8370146, Chile [2]Interdisciplinary Center for Aquaculture Research (INCAR), Victor Lamas 1290, P0 Box 160-C, Concepcion, Chile

出　　处：《Acta Biochimica et Biophysica Sinica》2015年第11期932-937,共6页生物化学与生物物理学报（英文版）

摘　　要：Lipopolysaccharide （LPS） is considered as a powerful inducer of muscle atrophy in higher verte- brates due to skeletal muscle cell recognition of the endotoxin and a consequent activation of cata- bolic signaling pathways. In contrast, there is no evidence of LPS directly inducing skeletal muscle atrophy in lower vertebrates, such as fish. For years it has been assumed that fish are resistant to LPS, mainly due to differences in the key features of toll-like receptor （TLR） signaling pathways when com- pared with mammals. In this study, we report that the stimulation of cultured rainbow trout （Oncor- hynchus mykiss） myotubes with LPS （100 ng/ml） resulted in a transient decrease in the pAkt/Akt ratio, a subsequent reduction in the pFoxO1/FoxO1 ratio, and a significant increase in atrogin-I tran- script expression. Preincubation with polymyxin B, an LPS-neutralizing agent, and 740 Y-P, an agon- ist of p85-PI3K, blocked the effects of LPS. Additionally, LPS treatment induced an increase in protein ubiquitination and a reduction in myotube diameter, both of which are associated with muscular at- rophy that is not observed under polymyxin B and 740 Y-P pretreatments. Finally, rainbow trout myo- tubes expressed the genes tlrl, tlr3, tlr5m, tlr8a1, tlr8a2, tlr9, and tlr22, with significantly increased expressions of tlr5m and tlr9 under LPS stimulation. These results indicate that LPS is an inducer of fish skeletal muscle atrophy and suggest that TLR5M and TLR9 may play important roles in detecting LPS, which supports for the first time the hypothesis that LPS is a direct inducer of skeletal muscle atrophy in teleost species.Lipopolysaccharide （LPS） is considered as a powerful inducer of muscle atrophy in higher verte- brates due to skeletal muscle cell recognition of the endotoxin and a consequent activation of cata- bolic signaling pathways. In contrast, there is no evidence of LPS directly inducing skeletal muscle atrophy in lower vertebrates, such as fish. For years it has been assumed that fish are resistant to LPS, mainly due to differences in the key features of toll-like receptor （TLR） signaling pathways when com- pared with mammals. In this study, we report that the stimulation of cultured rainbow trout （Oncor- hynchus mykiss） myotubes with LPS （100 ng/ml） resulted in a transient decrease in the pAkt/Akt ratio, a subsequent reduction in the pFoxO1/FoxO1 ratio, and a significant increase in atrogin-I tran- script expression. Preincubation with polymyxin B, an LPS-neutralizing agent, and 740 Y-P, an agon- ist of p85-PI3K, blocked the effects of LPS. Additionally, LPS treatment induced an increase in protein ubiquitination and a reduction in myotube diameter, both of which are associated with muscular at- rophy that is not observed under polymyxin B and 740 Y-P pretreatments. Finally, rainbow trout myo- tubes expressed the genes tlrl, tlr3, tlr5m, tlr8a1, tlr8a2, tlr9, and tlr22, with significantly increased expressions of tlr5m and tlr9 under LPS stimulation. These results indicate that LPS is an inducer of fish skeletal muscle atrophy and suggest that TLR5M and TLR9 may play important roles in detecting LPS, which supports for the first time the hypothesis that LPS is a direct inducer of skeletal muscle atrophy in teleost species.

关 键 词：LPS TELEOST skeletal muscle atrophy 

分 类 号：Q71[生物学—分子生物学] S562.035.3[农业科学—作物学]