RT Journal Article
T1 Role of Glucocorticoid Signaling and HDAC4 Activation in Diaphragm and Gastrocnemius Proteolytic Activity in Septic Rats.
A1 Moreno Ruperez, Álvaro
A1 Priego Cuadra, Teresa
A1 González Nicolás González, María Ángeles
A1 López-Calderón Barreda, Asunción
A1 Lázaro Fernández, Alberto
A1 Martín Velasco, Ana Isabel
AB Sepsis increases glucocorticoid and decreases IGF-1, leading to skeletal muscle wasting and cachexia. Muscle atrophy mainly takes place in locomotor muscles rather than in respiratory ones. Our study aimed to elucidate the mechanism responsible for this difference in muscle proteolysis, focusing on local inflammation and IGF-1 as well as on their glucocorticoid response and HDAC4-myogenin activation. Sepsis was induced in adult male rats by lipopolysaccharide (LPS) injection (10 mg/kg), and 24 h afterwards, rats were euthanized. LPS increased TNFα and IL-10 expression in both muscles studied, the diaphragm and gastrocnemius, whereas IL-6 and SOCS3 mRNA increased only in diaphragm. In comparison with gastrocnemius, diaphragm showed a lower increase in proteolytic marker expression (atrogin-1 and LC3b) and in LC3b protein lipidation after LPS administration. LPS increased the expression of glucocorticoid induced factors, KLF15 and REDD1, and decreased that of IGF-1 in gastrocnemius but not in the diaphragm. In addition, an increase in HDAC4 and myogenin expression was induced by LPS in gastrocnemius, but not in the diaphragm. In conclusion, the lower activation of both glucocorticoid signaling and HDAC4-myogenin pathways by sepsis can be one of the causes of lower sepsis-induced proteolysis in the diaphragm compared to gastrocnemius.
PB MDPI
SN 1422-0067
YR 2022
FD 2022-03-26
LK https://hdl.handle.net/20.500.14352/72281
UL https://hdl.handle.net/20.500.14352/72281
LA eng
NO Moreno Rupérez, Á., Priego Cuadra, T., González Nicolás González, M. Á. et al. «Role of Glucocorticoid Signaling and HDAC4 Activation in Diaphragm and Gastrocnemius Proteolytic Activity in Septic Rats». International Journal of Molecular Sciences, vol. 23, n.o 7, marzo de 2022, p. 3641. DOI.org (Crossref), https://doi.org/10.3390/ijms23073641.
NO Ministerio de Economía, Comercio y Empresa (España)
NO Fondo Europeo de Desarrollo Regional
NO Comisión Europea
NO Comunidad de Madrid
NO Fundación Senefro
NO Fundación Mutua Madrileña
DS Docta Complutense
RD 14 may 2025