The TORC1/P70S6K and TORC1/4EBP1 signaling pathways have a stronger contribution on skeletal muscle growth than MAPK/ERK in an early vertebrate: Differential involvement of the IGF system and atrogenes

Eduardo N. Fuentes, Ingibjörg Eir Einarsdottir, Rodolfo Paredes, Christian Hidalgo, Juan Antonio Valdes, Björn Thrandur Björnsson, Alfredo Molina

Resultado de la investigación: Article

15 Citas (Scopus)

Resumen

Knowledge about the underlying mechanisms, particularly the signaling pathways that account for muscle growth in vivo in early vertebrates is still scarce. Fish ( Paralichthys adspersus) were fasted for 3. weeks to induce a catabolic period of strong muscle atrophy. Subsequently, fish were refed for 2. weeks to induce compensatory muscle hypertrophy. During refeeding, the fish were treated daily with either rapamycin (TORC blocker), PD98059 (MEK blocker), or PBS (V; vehicle), or were untreated (C; control). Rapamycin and PD98059 differentially impaired muscle cellularity in vivo, growth performance, and the expression of growth-related genes, and the inhibition of TORC1 had a greater impact on fish muscle growth than the inhibition of MAPK. Blocking TORC1 inhibited the phosphorylation of P70S6K and 4EBP1, two downstream components activated by TORC1, thus affecting protein contents in muscle. Concomitantly, the gene expression in muscle of igf-1, 2 and igfbp-4, 5 was down-regulated while the expression of atrogin-1, murf-1, and igfbp-2, 3 was up-regulated. Muscle hypertrophy was abolished and muscle atrophy was promoted, which finally affected body weight. TORC2 complex was not affected by rapamycin. On the other hand, the PD98059 treatment triggered ERK inactivation, a downstream component activated by MEK. mRNA contents of igf-1 in muscle were down-regulated, and muscle hypertrophy was partially impaired. The present study provides the first direct data on the in vivo contribution of TORC1/P70S6K, TORC1/4EBP1, and MAPK/ERK signaling pathways in the skeletal muscle of an earlier vertebrate, and highlights the transcendental role of TORC1 in growth from the cellular to organism level.

Idioma originalEnglish
Páginas (desde-hasta)96-106
Número de páginas11
PublicaciónGeneral and Comparative Endocrinology
Volumen210
DOI
EstadoPublished - 1 ene 2015

Huella dactilar

70-kDa Ribosomal Protein S6 Kinases
skeletal muscle
Vertebrates
Skeletal Muscle
vertebrates
Muscles
muscles
Growth
Fishes
Sirolimus
hypertrophy
Hypertrophy
muscular atrophy
Muscular Atrophy
Mitogen-Activated Protein Kinase Kinases
fish
mechanistic target of rapamycin complex 1
MAP Kinase Signaling System
refeeding
growth retardation

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Endocrinology

Citar esto

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title = "The TORC1/P70S6K and TORC1/4EBP1 signaling pathways have a stronger contribution on skeletal muscle growth than MAPK/ERK in an early vertebrate: Differential involvement of the IGF system and atrogenes",
abstract = "Knowledge about the underlying mechanisms, particularly the signaling pathways that account for muscle growth in vivo in early vertebrates is still scarce. Fish ( Paralichthys adspersus) were fasted for 3. weeks to induce a catabolic period of strong muscle atrophy. Subsequently, fish were refed for 2. weeks to induce compensatory muscle hypertrophy. During refeeding, the fish were treated daily with either rapamycin (TORC blocker), PD98059 (MEK blocker), or PBS (V; vehicle), or were untreated (C; control). Rapamycin and PD98059 differentially impaired muscle cellularity in vivo, growth performance, and the expression of growth-related genes, and the inhibition of TORC1 had a greater impact on fish muscle growth than the inhibition of MAPK. Blocking TORC1 inhibited the phosphorylation of P70S6K and 4EBP1, two downstream components activated by TORC1, thus affecting protein contents in muscle. Concomitantly, the gene expression in muscle of igf-1, 2 and igfbp-4, 5 was down-regulated while the expression of atrogin-1, murf-1, and igfbp-2, 3 was up-regulated. Muscle hypertrophy was abolished and muscle atrophy was promoted, which finally affected body weight. TORC2 complex was not affected by rapamycin. On the other hand, the PD98059 treatment triggered ERK inactivation, a downstream component activated by MEK. mRNA contents of igf-1 in muscle were down-regulated, and muscle hypertrophy was partially impaired. The present study provides the first direct data on the in vivo contribution of TORC1/P70S6K, TORC1/4EBP1, and MAPK/ERK signaling pathways in the skeletal muscle of an earlier vertebrate, and highlights the transcendental role of TORC1 in growth from the cellular to organism level.",
keywords = "Atrophy, ERK, Hypertrophy, IGF system, Teleost fish, TORC",
author = "Fuentes, {Eduardo N.} and Einarsdottir, {Ingibj{\"o}rg Eir} and Rodolfo Paredes and Christian Hidalgo and Valdes, {Juan Antonio} and Bj{\"o}rnsson, {Bj{\"o}rn Thrandur} and Alfredo Molina",
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journal = "General and Comparative Endocrinology",
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T1 - The TORC1/P70S6K and TORC1/4EBP1 signaling pathways have a stronger contribution on skeletal muscle growth than MAPK/ERK in an early vertebrate

T2 - Differential involvement of the IGF system and atrogenes

AU - Fuentes, Eduardo N.

AU - Einarsdottir, Ingibjörg Eir

AU - Paredes, Rodolfo

AU - Hidalgo, Christian

AU - Valdes, Juan Antonio

AU - Björnsson, Björn Thrandur

AU - Molina, Alfredo

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Knowledge about the underlying mechanisms, particularly the signaling pathways that account for muscle growth in vivo in early vertebrates is still scarce. Fish ( Paralichthys adspersus) were fasted for 3. weeks to induce a catabolic period of strong muscle atrophy. Subsequently, fish were refed for 2. weeks to induce compensatory muscle hypertrophy. During refeeding, the fish were treated daily with either rapamycin (TORC blocker), PD98059 (MEK blocker), or PBS (V; vehicle), or were untreated (C; control). Rapamycin and PD98059 differentially impaired muscle cellularity in vivo, growth performance, and the expression of growth-related genes, and the inhibition of TORC1 had a greater impact on fish muscle growth than the inhibition of MAPK. Blocking TORC1 inhibited the phosphorylation of P70S6K and 4EBP1, two downstream components activated by TORC1, thus affecting protein contents in muscle. Concomitantly, the gene expression in muscle of igf-1, 2 and igfbp-4, 5 was down-regulated while the expression of atrogin-1, murf-1, and igfbp-2, 3 was up-regulated. Muscle hypertrophy was abolished and muscle atrophy was promoted, which finally affected body weight. TORC2 complex was not affected by rapamycin. On the other hand, the PD98059 treatment triggered ERK inactivation, a downstream component activated by MEK. mRNA contents of igf-1 in muscle were down-regulated, and muscle hypertrophy was partially impaired. The present study provides the first direct data on the in vivo contribution of TORC1/P70S6K, TORC1/4EBP1, and MAPK/ERK signaling pathways in the skeletal muscle of an earlier vertebrate, and highlights the transcendental role of TORC1 in growth from the cellular to organism level.

AB - Knowledge about the underlying mechanisms, particularly the signaling pathways that account for muscle growth in vivo in early vertebrates is still scarce. Fish ( Paralichthys adspersus) were fasted for 3. weeks to induce a catabolic period of strong muscle atrophy. Subsequently, fish were refed for 2. weeks to induce compensatory muscle hypertrophy. During refeeding, the fish were treated daily with either rapamycin (TORC blocker), PD98059 (MEK blocker), or PBS (V; vehicle), or were untreated (C; control). Rapamycin and PD98059 differentially impaired muscle cellularity in vivo, growth performance, and the expression of growth-related genes, and the inhibition of TORC1 had a greater impact on fish muscle growth than the inhibition of MAPK. Blocking TORC1 inhibited the phosphorylation of P70S6K and 4EBP1, two downstream components activated by TORC1, thus affecting protein contents in muscle. Concomitantly, the gene expression in muscle of igf-1, 2 and igfbp-4, 5 was down-regulated while the expression of atrogin-1, murf-1, and igfbp-2, 3 was up-regulated. Muscle hypertrophy was abolished and muscle atrophy was promoted, which finally affected body weight. TORC2 complex was not affected by rapamycin. On the other hand, the PD98059 treatment triggered ERK inactivation, a downstream component activated by MEK. mRNA contents of igf-1 in muscle were down-regulated, and muscle hypertrophy was partially impaired. The present study provides the first direct data on the in vivo contribution of TORC1/P70S6K, TORC1/4EBP1, and MAPK/ERK signaling pathways in the skeletal muscle of an earlier vertebrate, and highlights the transcendental role of TORC1 in growth from the cellular to organism level.

KW - Atrophy

KW - ERK

KW - Hypertrophy

KW - IGF system

KW - Teleost fish

KW - TORC

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U2 - 10.1016/j.ygcen.2014.10.012

DO - 10.1016/j.ygcen.2014.10.012

M3 - Article

C2 - 25449137

AN - SCOPUS:84911378040

VL - 210

SP - 96

EP - 106

JO - General and Comparative Endocrinology

JF - General and Comparative Endocrinology

SN - 0016-6480

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