Structural and molecular adaptations to dexamethasone and unacylated ghrelin administration in skeletal muscle of the mice

M Canepari, V Agoni, L Brocca, E Ghigo, M Gnesi, M A Minetto, R Bottinelli

Research output: Contribution to journalArticle

Abstract

The central goal of this study was to identify the primary mechanisms triggering steroid atrophy. Adaptations of soleus (Sol) and vastus lateralis (VL) muscles of C57BL/6 female mice were studied following 3, 7 and 15 days of daily intraperitoneal injection (5 mg kg-1 day-1) of dexamethasone (dEx) (chronic treatment) and 1, 3 and 10 hours after a single dEx injection (acute treatment). In the chronic treatment, analyses were performed 24 hours after the last injection. Gene expression of major components of the intracellular signalling pathways controlling mass and metabolism were assessed. Analyses were repeated following dEx and unacylated ghrelin (uAG) (100 μg kg-1day-1), co-administration. We found a significant VL fibres atrophy after 7 (13%) and 15 (28%) days and a Sol fibres atrophy (23%) after 15 days of dEx treatment. The acute treatment showed, in both muscles, several responses in most signalling pathways, among which the enhanced gene expression of Murf-1 (6-fold change in VL and 3-fold in Sol) and myostatin (6-fold change in VL and 20-fold in Sol). In Sol, uAG administration was able to fully counteract muscle atrophy and Murf-1 upregulation, but not the upregulation of myostatin, suggesting a causal relationship between muscle atrophy and Murf-1. Results indicate that: a) the primary mechanism triggering steroid atrophy is an early transient activation of Murf-1; b) uAG inhibits Murf-1 induction counteracting steroid atrophy. The present work contributes to the understanding of the complexity of the muscle response to glucocorticoids.

Original languageEnglish
JournalJournal of Physiology and Pharmacology
Volume69
Issue number2
DOIs
Publication statusPublished - Apr 2018

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Ghrelin
Dexamethasone
Atrophy
Quadriceps Muscle
Skeletal Muscle
Myostatin
Muscular Atrophy
Steroids
Muscles
Up-Regulation
Therapeutics
Gene Expression
Injections
Intraperitoneal Injections
Glucocorticoids

Keywords

  • Animals
  • Dexamethasone/pharmacology
  • Female
  • Forkhead Box Protein O3/genetics
  • Gene Expression Regulation/drug effects
  • Ghrelin/pharmacology
  • Glucocorticoids/pharmacology
  • Mice, Inbred C57BL
  • Muscle Proteins/genetics
  • Muscle, Skeletal/drug effects
  • Muscular Atrophy/drug therapy
  • RNA, Messenger/metabolism
  • SKP Cullin F-Box Protein Ligases/genetics
  • Tripartite Motif Proteins/genetics
  • Ubiquitin-Protein Ligases/genetics

Cite this

Structural and molecular adaptations to dexamethasone and unacylated ghrelin administration in skeletal muscle of the mice. / Canepari, M; Agoni, V; Brocca, L; Ghigo, E; Gnesi, M; Minetto, M A; Bottinelli, R.

In: Journal of Physiology and Pharmacology, Vol. 69, No. 2, 04.2018.

Research output: Contribution to journalArticle

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abstract = "The central goal of this study was to identify the primary mechanisms triggering steroid atrophy. Adaptations of soleus (Sol) and vastus lateralis (VL) muscles of C57BL/6 female mice were studied following 3, 7 and 15 days of daily intraperitoneal injection (5 mg kg-1 day-1) of dexamethasone (dEx) (chronic treatment) and 1, 3 and 10 hours after a single dEx injection (acute treatment). In the chronic treatment, analyses were performed 24 hours after the last injection. Gene expression of major components of the intracellular signalling pathways controlling mass and metabolism were assessed. Analyses were repeated following dEx and unacylated ghrelin (uAG) (100 μg kg-1day-1), co-administration. We found a significant VL fibres atrophy after 7 (13{\%}) and 15 (28{\%}) days and a Sol fibres atrophy (23{\%}) after 15 days of dEx treatment. The acute treatment showed, in both muscles, several responses in most signalling pathways, among which the enhanced gene expression of Murf-1 (6-fold change in VL and 3-fold in Sol) and myostatin (6-fold change in VL and 20-fold in Sol). In Sol, uAG administration was able to fully counteract muscle atrophy and Murf-1 upregulation, but not the upregulation of myostatin, suggesting a causal relationship between muscle atrophy and Murf-1. Results indicate that: a) the primary mechanism triggering steroid atrophy is an early transient activation of Murf-1; b) uAG inhibits Murf-1 induction counteracting steroid atrophy. The present work contributes to the understanding of the complexity of the muscle response to glucocorticoids.",
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T1 - Structural and molecular adaptations to dexamethasone and unacylated ghrelin administration in skeletal muscle of the mice

AU - Canepari, M

AU - Agoni, V

AU - Brocca, L

AU - Ghigo, E

AU - Gnesi, M

AU - Minetto, M A

AU - Bottinelli, R

PY - 2018/4

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N2 - The central goal of this study was to identify the primary mechanisms triggering steroid atrophy. Adaptations of soleus (Sol) and vastus lateralis (VL) muscles of C57BL/6 female mice were studied following 3, 7 and 15 days of daily intraperitoneal injection (5 mg kg-1 day-1) of dexamethasone (dEx) (chronic treatment) and 1, 3 and 10 hours after a single dEx injection (acute treatment). In the chronic treatment, analyses were performed 24 hours after the last injection. Gene expression of major components of the intracellular signalling pathways controlling mass and metabolism were assessed. Analyses were repeated following dEx and unacylated ghrelin (uAG) (100 μg kg-1day-1), co-administration. We found a significant VL fibres atrophy after 7 (13%) and 15 (28%) days and a Sol fibres atrophy (23%) after 15 days of dEx treatment. The acute treatment showed, in both muscles, several responses in most signalling pathways, among which the enhanced gene expression of Murf-1 (6-fold change in VL and 3-fold in Sol) and myostatin (6-fold change in VL and 20-fold in Sol). In Sol, uAG administration was able to fully counteract muscle atrophy and Murf-1 upregulation, but not the upregulation of myostatin, suggesting a causal relationship between muscle atrophy and Murf-1. Results indicate that: a) the primary mechanism triggering steroid atrophy is an early transient activation of Murf-1; b) uAG inhibits Murf-1 induction counteracting steroid atrophy. The present work contributes to the understanding of the complexity of the muscle response to glucocorticoids.

AB - The central goal of this study was to identify the primary mechanisms triggering steroid atrophy. Adaptations of soleus (Sol) and vastus lateralis (VL) muscles of C57BL/6 female mice were studied following 3, 7 and 15 days of daily intraperitoneal injection (5 mg kg-1 day-1) of dexamethasone (dEx) (chronic treatment) and 1, 3 and 10 hours after a single dEx injection (acute treatment). In the chronic treatment, analyses were performed 24 hours after the last injection. Gene expression of major components of the intracellular signalling pathways controlling mass and metabolism were assessed. Analyses were repeated following dEx and unacylated ghrelin (uAG) (100 μg kg-1day-1), co-administration. We found a significant VL fibres atrophy after 7 (13%) and 15 (28%) days and a Sol fibres atrophy (23%) after 15 days of dEx treatment. The acute treatment showed, in both muscles, several responses in most signalling pathways, among which the enhanced gene expression of Murf-1 (6-fold change in VL and 3-fold in Sol) and myostatin (6-fold change in VL and 20-fold in Sol). In Sol, uAG administration was able to fully counteract muscle atrophy and Murf-1 upregulation, but not the upregulation of myostatin, suggesting a causal relationship between muscle atrophy and Murf-1. Results indicate that: a) the primary mechanism triggering steroid atrophy is an early transient activation of Murf-1; b) uAG inhibits Murf-1 induction counteracting steroid atrophy. The present work contributes to the understanding of the complexity of the muscle response to glucocorticoids.

KW - Animals

KW - Dexamethasone/pharmacology

KW - Female

KW - Forkhead Box Protein O3/genetics

KW - Gene Expression Regulation/drug effects

KW - Ghrelin/pharmacology

KW - Glucocorticoids/pharmacology

KW - Mice, Inbred C57BL

KW - Muscle Proteins/genetics

KW - Muscle, Skeletal/drug effects

KW - Muscular Atrophy/drug therapy

KW - RNA, Messenger/metabolism

KW - SKP Cullin F-Box Protein Ligases/genetics

KW - Tripartite Motif Proteins/genetics

KW - Ubiquitin-Protein Ligases/genetics

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DO - 10.26402/jpp.2018.2.14

M3 - Article

C2 - 30045005

VL - 69

JO - Journal of Physiology and Pharmacology

JF - Journal of Physiology and Pharmacology

SN - 0867-5910

IS - 2

ER -