Openly accessible

NDRG2 promotes myoblast proliferation and caspase 3/7 activities during differentiation, and attenuates hydrogen peroxide - but not palmitate-induced toxicity

Anderson, Kimberley J., Russell, Aaron P. and Foletta, Victoria C. 2015, NDRG2 promotes myoblast proliferation and caspase 3/7 activities during differentiation, and attenuates hydrogen peroxide - but not palmitate-induced toxicity, FEBS open bio, vol. 5, no. 1, pp. 668-681, doi: 10.1016/j.fob.2015.08.001.

Attached Files
Name Description MIMEType Size Downloads
russell-ndrg2promotesmyoblast-2015.pdf Published version application/pdf 2.39MB 77

Title NDRG2 promotes myoblast proliferation and caspase 3/7 activities during differentiation, and attenuates hydrogen peroxide - but not palmitate-induced toxicity
Author(s) Anderson, Kimberley J.
Russell, Aaron P.ORCID iD for Russell, Aaron P. orcid.org/0000-0002-7323-9501
Foletta, Victoria C.ORCID iD for Foletta, Victoria C. orcid.org/0000-0002-5209-6134
Journal name FEBS open bio
Volume number 5
Issue number 1
Start page 668
End page 681
Total pages 14
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2015-01-01
ISSN 2211-5463
Keyword(s) Acta1, skeletal muscle alpha-actin
Akt, thymoma viral proto-oncogene
Apoptosis
Bax, Bcl-2-associated X protein
Bcl-2, B cell leukemia/lymphoma 2
Bcl-xL, Bcl-2-like 1
Caspase, apoptosis-related cysteine peptidase
Cdk, cyclin-dependent kinase
Ckm, muscle creatine kinase
Differentiation
ER stress
ER, endoplasmic reticulum
GRP78, glucose-regulated protein 78
H2O2, hydrogen peroxide
Lipotoxicity
MRFs, myogenic regulatory factors
Mcl-1, myeloid cell leukemia 1
Myf5, myogenic factor 5
Myh7, myosin, heavy polypeptide 7
MyoD, myogenic differentiation
Myoblast
Myotube
NDRG2
NDRG2, N-myc downstream-regulated gene 2
Oxidative stress
PA, palmitate
PARP, poly (ADP-ribose) polymerase family, member
PKCθ, protein kinase C theta
Proliferation
Rb, retinoblastoma
SGK1, serum- and glucocorticoid-inducible kinase 1
p21, p21 waf1/cip1
p27, p27 kip1
Summary The function of the stress-responsive N-myc downstream-regulated gene 2 (NDRG2) in the control of myoblast growth, and the amino acids contributing to its function, are not well characterized. Here, we investigated the effect of increased NDRG2 levels on the proliferation, differentiation and apoptosis in skeletal muscle cells under basal and stress conditions. NDRG2 overexpression increased C2C12 myoblast proliferation and the expression of positive cell cycle regulators, cdk2, cyclin B and cyclin D, and phosphorylation of Rb, while the serine/threonine-deficient NDRG2, 3A-NDRG2, had less effect. The onset of differentiation was enhanced by NDRG2 as determined through the myogenic regulatory factor expression profiles and myocyte fusion index. However, the overall level of differentiation in myotubes was not different. While NDRG2 up-regulated caspase 3/7 activities during differentiation, no increase in apoptosis was measured by TUNEL assay or through cleavage of caspase 3 and PARP proteins. During H2O2 treatment to induce oxidative stress, NDRG2 helped protect against the loss of proliferation and ER stress as measured by GRP78 expression with 3A-NDRG2 displaying less protection. NDRG2 also attenuated apoptosis by reducing cleavage of PARP and caspase 3 and expression of pro-apoptotic Bax while enhancing the pro-survival Bcl-2 and Bcl-xL levels. In contrast, Mcl-1 was not altered, and NDRG2 did not protect against palmitate-induced lipotoxicity. Our findings show that NDRG2 overexpression increases myoblast proliferation and caspase 3/7 activities without increasing overall differentiation. Furthermore, NDRG2 attenuates H2O2-induced oxidative stress and specific serine and threonine amino acid residues appear to contribute to its function in muscle cells.
Language eng
DOI 10.1016/j.fob.2015.08.001
Field of Research 110699 Human Movement and Sports Science not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution Non-Commercial No-Derivatives licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30080622

Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 12 times in TR Web of Science
Scopus Citation Count Cited 12 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 476 Abstract Views, 78 File Downloads  -  Detailed Statistics
Created: Fri, 08 Jan 2016, 15:19:28 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.