PMID- 12087247
OWN - NLM
STAT- MEDLINE
DCOM- 20020718
LR  - 20220228
IS  - 0032-1052 (Print)
IS  - 0032-1052 (Linking)
VI  - 110
IP  - 1
DP  - 2002 Jul
TI  - Skeletal muscle denervation increases satellite cell susceptibility to apoptosis.
PG  - 160-8
AB  - Peripheral motor nerve trauma severely compromises skeletal muscle contractile 
      function. Satellite cells respond to denervation by dividing multiple times, 
      ultimately fusing with other satellite cells or myocytes to form new muscle 
      fibers. After chronic denervation, satellite cell numbers decline dramatically, 
      impairing the ability to regenerate and repair myofibers. This satellite cell 
      depletion may contribute to the mechanical deficit observed in denervated or 
      reinnervated muscle. Apoptosis, an evolutionarily conserved form of cell suicide, 
      is a potential mechanism for satellite cell depletion in denervated skeletal 
      muscle. This work tested the hypothesis that skeletal muscle denervation 
      increases satellite cell susceptibility to apoptotic cell death. Adult rats 
      underwent sciatic nerve transection to denervate the distal hindlimb musculature; 
      rats of similar age without the operation served as controls. Two, 6, 10, or 20 
      weeks after denervation (n = 6 each group), the gastrocnemius and soleus were 
      excised, enzymatically digested, and plated for satellite cell culture. After 
      reaching 95 percent confluence, satellite cells were treated for 24 hours with 
      tumor necrosis factor-alpha (20 ng/ml) and actinomycin D (250 ng/ml), known 
      pro-apoptotic agents. Immunostaining for activated caspases, terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and 
      hematoxylin and eosin staining were performed to identify apoptotic satellite 
      cells. Percentages of apoptotic cells were quantified histomorphometrically. In 
      addition, the presence or absence of bcl-2 and bax was determined by Western blot 
      analysis of control, 6 weeks of denervation, and 10 weeks of denervation 
      specimens. At 6 and 10 weeks after nerve transection, TUNEL and caspase activity 
      were increased more than two-fold in satellite cells isolated from denervated 
      muscle compared with those isolated from control muscle (p < 0.05). In all 
      experimental groups, retention of adherence to the collagen-coated substrate was 
      strongly associated with satellite cell survival. Western blot analysis revealed 
      that adherent satellite cells from all groups expressed both bcl-2 and bax. These 
      data support the authors' hypothesis that skeletal muscle denervation increases 
      satellite cell susceptibility to apoptotic cell death. Apoptosis may play a 
      causative role in the depletion of satellite cells in long-term denervated 
      skeletal muscle.
FAU - Jejurikar, Sameer S
AU  - Jejurikar SS
AD  - Section of Plastic and Reconstructive Surgery, Department of Surgery, University 
      of Michigan Medical Center 2130 Taubman Health Care Center, 1500 East Medical 
      Center Drive, Ann Arbor, MI 48109-0340, USA.
FAU - Marcelo, Cynthia L
AU  - Marcelo CL
FAU - Kuzon, William M Jr
AU  - Kuzon WM Jr
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Plast Reconstr Surg
JT  - Plastic and reconstructive surgery
JID - 1306050
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Blotting, Western
MH  - In Situ Nick-End Labeling
MH  - *Muscle Denervation
MH  - Muscle, Skeletal/*innervation
MH  - Rats
MH  - Rats, Inbred F344
MH  - Satellite Cells, Perineuronal/*pathology
EDAT- 2002/06/28 10:00
MHDA- 2002/07/19 10:01
CRDT- 2002/06/28 10:00
PHST- 2002/06/28 10:00 [pubmed]
PHST- 2002/07/19 10:01 [medline]
PHST- 2002/06/28 10:00 [entrez]
AID - 10.1097/00006534-200207000-00027 [doi]
PST - ppublish
SO  - Plast Reconstr Surg. 2002 Jul;110(1):160-8. doi: 
      10.1097/00006534-200207000-00027.