Reduction of myoblast differentiation following multiple population doublings in mouse C2 C12 cells: a model to investigate ageing?

2.50
Hdl Handle:
http://hdl.handle.net/10547/225932
Title:
Reduction of myoblast differentiation following multiple population doublings in mouse C2 C12 cells: a model to investigate ageing?
Authors:
Sharples, Adam P. ( 0000-0003-1526-9400 ) ; Al-Shanti, Nasser; Lewis, Mark P.; Stewart, Claire E.
Abstract:
Ageing skeletal muscle displays declines in size, strength, and functional capacity. Given the acknowledged role that the systemic environment plays in reduced regeneration (Conboy et al. [2005] Nature 433: 760-764), the role of resident satellite cells (termed myoblasts upon activation) is relatively dismissed, where, multiple cellular divisions in-vivo throughout the lifespan could also impact on muscular deterioration. Using a model of multiple population doublings (MPD) in-vitro thus provided a system in which to investigate the direct impact of extensive cell duplications on muscle cell behavior. C(2) C(12) mouse skeletal myoblasts (CON) were used fresh or following 58 population doublings (MPD). As a result of multiple divisions, reduced morphological and biochemical (creatine kinase, CK) differentiation were observed. Furthermore, MPD cells had significantly increased cells in the S and decreased cells in the G1 phases of the cell cycle versus CON, following serum withdrawal. These results suggest continued cycling rather than G1 exit and thus reduced differentiation (myotube atrophy) occurs in MPD muscle cells. These changes were underpinned by significant reductions in transcript expression of: IGF-I and myogenic regulatory factors (myoD and myogenin) together with elevated IGFBP5. Signaling studies showed that decreased differentiation in MPD was associated with decreased phosphorylation of Akt, and with later increased phosphorylation of JNK1/2. Chemical inhibition of JNK1/2 (SP600125) in MPD cells increased IGF-I expression (non-significantly), however, did not enhance differentiation. This study provides a potential model and molecular mechanisms for deterioration in differentiation capacity in skeletal muscle cells as a consequence of multiple population doublings that would potentially contribute to the ageing process.
Affiliation:
University of Bedfordshire
Citation:
Sharples A.P., Al-Shanti N., Lewis M.P., and Stewart C.E., (2011) 'Reduction of myoblast differentiation following multiple population doublings in mouse C2 C12 cells: a model to investigate ageing?', Journal of Cellular Biochemistry, 112(12) pp.3773-85.
Journal:
Journal of Cellular Biochemistry
Issue Date:
Dec-2011
URI:
http://hdl.handle.net/10547/225932
DOI:
10.1002/jcb.23308
PubMed ID:
21826704
Type:
Article
Language:
en
ISSN:
1097-4644
Appears in Collections:
Muscle Cellular and Molecular Physiology

Full metadata record

DC FieldValue Language
dc.contributor.authorSharples, Adam P.en_GB
dc.contributor.authorAl-Shanti, Nasseren_GB
dc.contributor.authorLewis, Mark P.en_GB
dc.contributor.authorStewart, Claire E.en_GB
dc.date.accessioned2012-05-25T08:53:26Z-
dc.date.available2012-05-25T08:53:26Z-
dc.date.issued2011-12-
dc.identifier.citationSharples A.P., Al-Shanti N., Lewis M.P., and Stewart C.E., (2011) 'Reduction of myoblast differentiation following multiple population doublings in mouse C2 C12 cells: a model to investigate ageing?', Journal of Cellular Biochemistry, 112(12) pp.3773-85.en_GB
dc.identifier.issn1097-4644-
dc.identifier.pmid21826704-
dc.identifier.doi10.1002/jcb.23308-
dc.identifier.urihttp://hdl.handle.net/10547/225932-
dc.description.abstractAgeing skeletal muscle displays declines in size, strength, and functional capacity. Given the acknowledged role that the systemic environment plays in reduced regeneration (Conboy et al. [2005] Nature 433: 760-764), the role of resident satellite cells (termed myoblasts upon activation) is relatively dismissed, where, multiple cellular divisions in-vivo throughout the lifespan could also impact on muscular deterioration. Using a model of multiple population doublings (MPD) in-vitro thus provided a system in which to investigate the direct impact of extensive cell duplications on muscle cell behavior. C(2) C(12) mouse skeletal myoblasts (CON) were used fresh or following 58 population doublings (MPD). As a result of multiple divisions, reduced morphological and biochemical (creatine kinase, CK) differentiation were observed. Furthermore, MPD cells had significantly increased cells in the S and decreased cells in the G1 phases of the cell cycle versus CON, following serum withdrawal. These results suggest continued cycling rather than G1 exit and thus reduced differentiation (myotube atrophy) occurs in MPD muscle cells. These changes were underpinned by significant reductions in transcript expression of: IGF-I and myogenic regulatory factors (myoD and myogenin) together with elevated IGFBP5. Signaling studies showed that decreased differentiation in MPD was associated with decreased phosphorylation of Akt, and with later increased phosphorylation of JNK1/2. Chemical inhibition of JNK1/2 (SP600125) in MPD cells increased IGF-I expression (non-significantly), however, did not enhance differentiation. This study provides a potential model and molecular mechanisms for deterioration in differentiation capacity in skeletal muscle cells as a consequence of multiple population doublings that would potentially contribute to the ageing process.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Journal of cellular biochemistryen_GB
dc.subject.meshAging-
dc.subject.meshAnimals-
dc.subject.meshBase Sequence-
dc.subject.meshCell Cycle-
dc.subject.meshCell Differentiation-
dc.subject.meshCell Line-
dc.subject.meshDNA Primers-
dc.subject.meshFlow Cytometry-
dc.subject.meshMice-
dc.subject.meshMicroscopy, Fluorescence-
dc.subject.meshMuscle, Skeletal-
dc.subject.meshMyoblasts-
dc.subject.meshPhosphorylation-
dc.subject.meshProtein Kinases-
dc.subject.meshRNA, Messenger-
dc.subject.meshReal-Time Polymerase Chain Reaction-
dc.titleReduction of myoblast differentiation following multiple population doublings in mouse C2 C12 cells: a model to investigate ageing?en
dc.typeArticleen
dc.contributor.departmentUniversity of Bedfordshireen_GB
dc.identifier.journalJournal of Cellular Biochemistryen_GB

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