PMID- 22552967
OWN - NLM
STAT- MEDLINE
DCOM- 20121116
LR  - 20120712
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 113
IP  - 9
DP  - 2012 Sep
TI  - MmNEU3 sialidase over-expression in C2C12 myoblasts delays differentiation and 
      induces hypertrophic myotube formation.
PG  - 2967-78
LID - 10.1002/jcb.24174 [doi]
AB  - Several factors affect the skeletal muscle differentiation process, in particular 
      modifications of cell-cell contact, cell adhesion, and plasma membrane 
      characteristics. In order to support the role of the plasma membrane-associated 
      sialidase NEU3 in skeletal muscle differentiation and to analyse which events of 
      the process are mainly affected by this sialidase, we decided to stably 
      over-express MmNEU3 in C2C12 cells by a lentiviral vector and to investigate cell 
      behavior during the differentiation process. Vitally stained C2C12 and NEU3 
      over-expressing cells were counted to reveal modifications in differentiation 
      induction. We found that NEU3 over-expressing cells remained proliferative longer 
      than control cells and delayed the onset of differentiation. Expression of p21, 
      myogenic transcription factors, and myosin heavy chain (MHC), assessed by real 
      time PCR, confirmed this behavior. In particular, no MHC-positive myotubes were 
      present in NEU3 over-expressing cells as compared to wild type C2C12 cells at day 
      3 of differentiation. Moreover, NEU3 over-expressing cells completed the 
      differentiation process very quickly and formed hypertrophic myotubes. Analysis 
      of MAPK/ERK pathway activation showed an increased ERK 1/2 phosphorylation in 
      NEU3 over-expressing cells at the beginning of differentiation. We postulate that 
      sialidase NEU3, decreasing plasma membrane ganglioside GM3 content, affects the 
      EGF receptor and the downstream signaling pathways, promoting proliferation and 
      delaying differentiation. Furthermore NEU3 improves myoblast fusion probably via 
      neural-cell adhesion molecule (NCAM) desialylation. Therefore, this work further 
      supports the central role of NEU3 as a key modulator in skeletal muscle 
      differentiation, particularly in the myoblast fusion step.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Papini, Nadia
AU  - Papini N
AD  - Department of Medical Chemistry, University of Milan, 20090 Milan, Italy.
FAU - Anastasia, Luigi
AU  - Anastasia L
FAU - Tringali, Cristina
AU  - Tringali C
FAU - Dileo, Loredana
AU  - Dileo L
FAU - Carubelli, Ivan
AU  - Carubelli I
FAU - Sampaolesi, Maurilio
AU  - Sampaolesi M
FAU - Monti, Eugenio
AU  - Monti E
FAU - Tettamanti, Guido
AU  - Tettamanti G
FAU - Venerando, Bruno
AU  - Venerando B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (G(M3) Ganglioside)
RN  - EC 3.2.1.18 (Neu3 protein, mouse)
RN  - EC 3.2.1.18 (Neuraminidase)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/genetics/*physiology
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - Chromatography, High Pressure Liquid
MH  - G(M3) Ganglioside/metabolism
MH  - Immunoblotting
MH  - Mice
MH  - Muscle Fibers, Skeletal/*cytology/*metabolism
MH  - Muscle, Skeletal/cytology/metabolism
MH  - Myoblasts/*cytology/*metabolism
MH  - Neuraminidase/genetics/*metabolism
MH  - Phosphorylation
MH  - Polymerase Chain Reaction
EDAT- 2012/05/04 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/05/04 06:00
PHST- 2012/05/04 06:00 [entrez]
PHST- 2012/05/04 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - 10.1002/jcb.24174 [doi]
PST - ppublish
SO  - J Cell Biochem. 2012 Sep;113(9):2967-78. doi: 10.1002/jcb.24174.