RESUMEN
Toll-like receptor 5 is a pattern-recognition receptor for bacterial flagellin. We previously reported that a single nucleotide polymorphism (SNP) of swine TLR5, C1205T, impairs recognition of Salmonella typhimurium (ST) flagellin and ethanol-killed Salmonella Choleraesuis (SC). In the present study, weaned, specific pathogen-free (SPF) Landrace piglets with CC, CT or TT genotypes were orally infected with ST (L-3569 strain) to determine the effect of this specific SNP on ST infection in vivo. Eighteen ST-infected piglets (six each with CC, CT, or TT) exhibited fever and diarrhea for 1 week after infection. TT piglets had the longest duration of fever. TT piglets had the greatest mean diarrhea score during the experimental period, followed by CT and CC piglets. Fecal ST shedding was greater in CT and TT pigs than CC pigs from 2 days after infection. Serum haptoglobin concentration increased in ST-infected piglets and to greater extents in CT and TT pigs than CC pigs. Daily weight gain was lower in infected pigs, particularly TT piglets, than control pigs. To the best of our knowledge, this study is the first to demonstrate that impairment of TLR recognition affects pig susceptibility to disease in vivo. Thus, piglets with the T allele of swine TLR5 (C1205T) exhibit impaired resistance to ST infection. Furthermore, elimination of the T allele of this SNP from Landrace pigs would lead to enhancement of their resistance to ST infection.
Asunto(s)
Polimorfismo de Nucleótido Simple/inmunología , Salmonella typhimurium/inmunología , Salmonella typhimurium/patogenicidad , Enfermedades de los Porcinos/inmunología , Receptor Toll-Like 5/inmunología , Animales , Diarrea/inmunología , Diarrea/microbiología , Diarrea/veterinaria , Heces/microbiología , Genotipo , Haptoglobinas/análisis , Interleucina-1beta/sangre , Ganglios Linfáticos/microbiología , Ganglios Linfáticos/patología , Masculino , Salmonelosis Animal/inmunología , Salmonelosis Animal/microbiología , Salmonelosis Animal/patología , Porcinos , Enfermedades de los Porcinos/microbiología , DesteteRESUMEN
In skeletal muscle, AMP-activated protein kinase (AMPK) is a metabolic master switch regulating glucose and lipid metabolism. Recently, AMPK has been implicated in the control of protein synthesis in skeletal muscle, but the effect of AMPK activation on myofibrillar protein degradation has yet to be elucidated. The present study was designed to examine the effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR)-induced AMPK signaling on effector mechanisms of myofibrillar protein degradation and the expression of atrophy-related genes (atrogin-1/MAFbx, MuRF1, proteasome C2 subunit, calpains, cathepsin B, and caspase-3) in C2C12 myotubes. AICAR stimulated myofibrillar protein degradation (as measured by N(tau)-methylhistidine release), while also increasing the levels of atrogin-1/MAFbx and MuRF1 mRNA, but the expression of other atrophy-related genes was not enhanced by AICAR treatment in C2C12 myotubes. AICAR also stimulated the level of FOXO transcription factors mRNA and protein in C2C12 myotubes. These results indicate that activation of AMPK stimulates myofibrillar protein degradation through the expression of atrogin-1/MAFbx and MuRF1 by increasing FOXO transcription factors in skeletal muscles.
Asunto(s)
Factores de Transcripción Forkhead/fisiología , Complejos Multienzimáticos/fisiología , Fibras Musculares Esqueléticas/enzimología , Proteínas Musculares/genética , Atrofia Muscular/enzimología , Miofibrillas/metabolismo , Proteínas Serina-Treonina Quinasas/fisiología , Proteínas Ligasas SKP Cullina F-box/genética , Ubiquitina-Proteína Ligasas/genética , Proteínas Quinasas Activadas por AMP , Aminoimidazol Carboxamida/análogos & derivados , Animales , Línea Celular , Activación Enzimática/fisiología , Regulación de la Expresión Génica/fisiología , Ratones , Proteínas Musculares/biosíntesis , Fosforilación , Ribonucleótidos/fisiología , Proteínas Ligasas SKP Cullina F-box/biosíntesis , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas/biosíntesisRESUMEN
This experiment was conducted to study the effects of fasting and refeeding on expression of the atrogin-1 and Akt/FOXO signaling pathway in skeletal muscle of chicks. Chicks were fasted for 24 h and refed for 2 h. Atrogin-1 mRNA expression was increased by fasting, and their increment was reduced by refeeding. Phosphorylations of Akt and FOXO1 were not decreased by fasting, but, they were increased by refeeding. These results indicate that refeeding stimulates phosphorylation of Akt/FOXO, resulting in a decrease in atrogin-1 expression in skeletal muscle of chicks.
Asunto(s)
Alimentación Animal , Factores de Transcripción Forkhead/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Ligasas SKP Cullina F-box/metabolismo , Transducción de Señal , Animales , Pollos , Proteínas Musculares/genética , Fosforilación , ARN Mensajero/genética , Proteínas Ligasas SKP Cullina F-box/genéticaRESUMEN
We examined the effects of orally administrated amino acids on myfibrillar proteolysis in food-deprived chicks. Plasma N(tau)-methylhistidine concentration, as an index of myofibrillar proteolysis, was decreased by the administration of Glu, Gly, Ala, Leu, Ile, Ser, Thr, Met, Trp, Asn, Gln, Pro, Lys and Arg but not by Asp, Val, Phe, Tyr or His to chicks. Orally administrated Cys was fatal to chicks. These results indicate that oral Glu, Gly, Ala, Leu, Ile, Ser, Thr, Met, Trp, Asn, Gln, Pro, Lys and Arg administration suppressed myofibrillar proteolysis in chicks.
