PMID- 21607286
OWN - NLM
STAT- MEDLINE
DCOM- 20120325
LR  - 20211203
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 17
IP  - 9-10
DP  - 2011 Sep-Oct
TI  - Rapamycin ameliorates dystrophic phenotype in mdx mouse skeletal muscle.
PG  - 917-24
LID - 10.2119/molmed.2010.00256 [doi]
AB  - Duchenne muscular dystrophy (DMD) is an X-linked, lethal, degenerative disease 
      that results from mutations in the dystrophin gene, causing necrosis and 
      inflammation in skeletal muscle tissue. Treatments that reduce muscle fiber 
      destruction and immune cell infiltration can ameliorate DMD pathology. We treated 
      the mdx mouse, a model for DMD, with the immunosuppressant drug rapamycin (RAPA) 
      both locally and systemically to examine its effects on dystrophic mdx muscles. 
      We observed a significant reduction of muscle fiber necrosis in treated mdx mouse 
      tibialis anterior (TA) and diaphragm (Dia) muscles 6 wks post-treatment. This 
      effect was associated with a significant reduction in infiltration of effector 
      CD4(+) and CD8(+) T cells in skeletal muscle tissue, while Foxp3(+) regulatory T 
      cells were preserved. Because RAPA exerts its effects through the mammalian 
      target of RAPA (mTOR), we studied the activation of mTOR in mdx TA and Dia with 
      and without RAPA treatment. Surprisingly, mTOR activation levels in mdx TA were 
      not different from control C57BL/10 (B10). However, mTOR activation was different 
      in Dia between mdx and B10; mTOR activation levels did not rise between 6 and 12 
      wks of age in mdx Dia muscle, whereas a rise in mTOR activation level was 
      observed in B10 Dia muscle. Furthermore, mdx Dia, but not TA, muscle mTOR 
      activation was responsive to RAPA treatment.
FAU - Eghtesad, Saman
AU  - Eghtesad S
AD  - Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
FAU - Jhunjhunwala, Siddharth
AU  - Jhunjhunwala S
FAU - Little, Steven R
AU  - Little SR
FAU - Clemens, Paula R
AU  - Clemens PR
LA  - eng
GR  - F31 NS056780/NS/NINDS NIH HHS/United States
GR  - KL2 RR024154/RR/NCRR NIH HHS/United States
GR  - F31-NS056780-01A2/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20110520
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (Immunosuppressive Agents)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - CD4-Positive T-Lymphocytes/drug effects/metabolism
MH  - CD8-Positive T-Lymphocytes/drug effects/metabolism
MH  - Diaphragm/drug effects/metabolism/pathology
MH  - Disease Models, Animal
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred mdx
MH  - Muscle Fibers, Skeletal/*drug effects/metabolism/pathology
MH  - Muscle, Skeletal/*drug effects/metabolism/pathology
MH  - Muscular Dystrophy, Animal/metabolism/pathology/*prevention & control
MH  - Muscular Dystrophy, Duchenne/metabolism/pathology/prevention & control
MH  - Phosphorylation/drug effects
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Time Factors
PMC - PMC3188871
EDAT- 2011/05/25 06:00
MHDA- 2012/03/27 06:00
PMCR- 2011/05/20
CRDT- 2011/05/25 06:00
PHST- 2010/12/08 00:00 [received]
PHST- 2011/05/19 00:00 [accepted]
PHST- 2011/05/25 06:00 [entrez]
PHST- 2011/05/25 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
PHST- 2011/05/20 00:00 [pmc-release]
AID - molmed.2010.00256 [pii]
AID - 10_256_eghtesad [pii]
AID - 10.2119/molmed.2010.00256 [doi]
PST - ppublish
SO  - Mol Med. 2011 Sep-Oct;17(9-10):917-24. doi: 10.2119/molmed.2010.00256. Epub 2011 
      May 20.