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Expression and phosphorylation of eukaryotic translation initiation factor 4-gamma (eIF4G) in denervated atrophic and hypertrophic mouse skeletal muscle
Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
2015 (engelsk)Inngår i: Cell Biology International, ISSN 1065-6995, E-ISSN 1095-8355, Vol. 39, nr 4, s. 496-501Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The eukaryotic translation initiation factor 4-gamma (eIF4G) is important for the initiation of protein synthesis and phosphorylation on S1108 regulates this function of eIF4G. Thus, increased phosphorylation has been reported in conditions associated with increased protein synthesis such as meal feeding and insulin/IGF-1 treatment whereas decreased phosphorylation occurs following starvation, dexamethasone treatment, in sepsis and in atrophic denervated hind-limb muscle. The aim of the present study was to test the hypothesis that S1108 phosphorylation of eIF4G is differentially affected in denervated atrophic hind-limb muscles and denervated hypertrophic hemidiaphragm muscle. Protein expression and phosphorylation in innervated and 6-days denervated atrophic hind-limb muscles (pooled gastrocnemius and soleus) and hypertrophic hemidiaphragms were studied semi-quantitatively using Western blots. Total expression of eIF4G did not change in denervated hind-limb muscles but increased about 77% in denervated hemidiaphragm. S1108 phosphorylated eIF4G decreased about 64% in denervated hind-limb muscles but increased about 1.3-fold in denervated hemidiaphragm. The ratio of S1108 phosphorylated eIF4G to total eIF4G decreased about 60% in denervated hind-limb muscles but no statistically significant change was observed in denervated hemidiaphragm. The differential effect of denervation on eIF4G expression and S1108 phosphorylation in hemidiaphragm (hypertrophic) and hind-limb muscle (atrophic) may represent a regulatory mechanism that helps clarify the differential response of these muscles following denervation.

sted, utgiver, år, opplag, sider
2015. Vol. 39, nr 4, s. 496-501
HSV kategori
Forskningsprogram
Naturvetenskap, Biomedicinsk vetenskap
Identifikatorer
URN: urn:nbn:se:lnu:diva-37958DOI: 10.1002/cbin.10402ISI: 000351678000017PubMedID: 25623635Scopus ID: 2-s2.0-84925292774OAI: oai:DiVA.org:lnu-37958DiVA, id: diva2:759752
Tilgjengelig fra: 2014-10-31 Laget: 2014-10-31 Sist oppdatert: 2017-12-05bibliografisk kontrollert
Inngår i avhandling
1. Signaling factors related to atrophy and hypertrophy in denervated skeletal muscle
Åpne denne publikasjonen i ny fane eller vindu >>Signaling factors related to atrophy and hypertrophy in denervated skeletal muscle
2014 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The human body consists of about 40 % skeletal muscles which control the body’s movement, ability to stand up, force generation, locomotion, heat production and are also the body’s protein reservoir. Muscle mass is controlled by the relationship between protein synthesis and protein degradation. Atrophy, a decrease in muscle mass, can be trigged by disuse, immobilization, inflammation and cancer. Hypertrophy, an increase in muscle mass, can occur after increased mechanical load, high usage and/or anabolic stimulation. The aim of this thesis was to investigate changes in expression and post translational modifications of some factors involved in the regulation of protein synthesis and protein degradation in 6-days denervated atrophic hind-limb muscles (anterior tibial and pooled gastrocnemius and soleus muscles) and in 6-days denervated hypertrophic hemidiaphragm muscle in mice. Protein expression and post translational modifications were studied semi-quantitatively using Western blots with whole muscle homogenates and separated nuclear and cytosolic fractions from both innervated and denervated muscles.  An increase in protein synthesis after denervation in both atrophic and hypertrophic muscles was suggested after studies of factors downstream of mTOR (paper I).  Other results suggest that FoxO1 and MuRF1 (paper II) participate in the tissue remodeling that occurs after denervation. A differential response of MK2 phosphorylation in denervated hypertrophic and atrophic muscles was confirmed (paper III). An increase in phosphorylation of the MK2 substrate Hsp 25 in all denervated muscles studied (paper III) indicates that other factors than MK2 are involved in regulating this phosphorylation. eIF4G phosphorylation at S1108 was investigated (paper IV) and a decrease was observed in atrophic muscle but an increase in hypertrophic muscle. The results in this thesis suggest that there are several factors that control protein degradation and protein synthesis in denervated atrophic and hypertrophic skeletal muscles. This is an intricate labyrinth with many different cell signaling factors, the function of which are still far from fully understood.

sted, utgiver, år, opplag, sider
Växjö: Linnaeus University Press, 2014. s. 96
Serie
Linnaeus University Dissertations ; 198/2014
Emneord
Atrophy, Hypertrophy, Skeletal muscle, Denervation, Protein synthesis, Protein degradation
HSV kategori
Forskningsprogram
Naturvetenskap, Biomedicinsk vetenskap
Identifikatorer
urn:nbn:se:lnu:diva-37670 (URN)978-91-87925-26-9 (ISBN)
Disputas
2014-11-21, N2007, Västergård, Smålandsgatan 26E, Kalmar, 09:00 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2014-11-03 Laget: 2014-10-15 Sist oppdatert: 2015-01-14bibliografisk kontrollert

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