Myostatin augments muscle-specific ring finger protein-1 expression through an NF-kB independent mechanism in SMAD3 null muscle.

Details

Serval ID
serval:BIB_6B78A3A04138
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Myostatin augments muscle-specific ring finger protein-1 expression through an NF-kB independent mechanism in SMAD3 null muscle.
Journal
Molecular Endocrinology
Author(s)
Sriram S., Subramanian S., Juvvuna P.K., Ge X., Lokireddy S., McFarlane C.D., Wahli W., Kambadur R., Sharma M.
ISSN
1944-9917 (Electronic)
ISSN-L
0888-8809
Publication state
Published
Issued date
2014
Volume
28
Number
3
Pages
317-330
Language
english
Abstract
Smad (Sma and Mad-related protein) 2/3 are downstream signaling molecules for TGF-β and myostatin (Mstn). Recently, Mstn was shown to induce reactive oxygen species (ROS) in skeletal muscle via canonical Smad3, nuclear factor-κB, and TNF-α pathway. However, mice lacking Smad3 display skeletal muscle atrophy due to increased Mstn levels. Hence, our aims were first to investigate whether Mstn induced muscle atrophy in Smad3(-/-) mice by increasing ROS and second to delineate Smad3-independent signaling mechanism for Mstn-induced ROS. Herein we show that Smad3(-/-) mice have increased ROS levels in skeletal muscle, and inactivation of Mstn in these mice partially ablates the oxidative stress. Furthermore, ROS induction by Mstn in Smad3(-/-) muscle was not via nuclear factor-κB (p65) signaling but due to activated p38, ERK MAPK signaling and enhanced IL-6 levels. Consequently, TNF-α, nicotinamide adenine dinucleotide phosphate oxidase, and xanthine oxidase levels were up-regulated, which led to an increase in ROS production in Smad3(-/-) skeletal muscle. The exaggerated ROS in the Smad3(-/-) muscle potentiated binding of C/EBP homology protein transcription factor to MuRF1 promoter, resulting in enhanced MuRF1 levels leading to muscle atrophy.
Pubmed
Web of science
Open Access
Yes
Create date
10/04/2014 8:48
Last modification date
20/08/2019 15:25
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