PMID- 17068216
OWN - NLM
STAT- MEDLINE
DCOM- 20070322
LR  - 20211203
IS  - 8750-7587 (Print)
IS  - 0161-7567 (Linking)
VI  - 102
IP  - 2
DP  - 2007 Feb
TI  - Rapamycin inhibits the growth and muscle-sparing effects of clenbuterol.
PG  - 740-7
AB  - Clenbuterol and other beta2-adrenergic agonists are effective at inducing muscle 
      growth and attenuating muscle atrophy through unknown mechanisms. This study 
      tested the hypothesis that clenbuterol-induced growth and muscle sparing is 
      mediated through the activation of Akt and mammalian target of rapamycin (mTOR) 
      signaling pathways. Clenbuterol was administered to normal weight-bearing adult 
      rats to examine the growth-inducing effects and to adult rats undergoing muscle 
      atrophy as the result of hindlimb suspension or denervation to examine the 
      muscle-sparing effects. The pharmacological inhibitor rapamycin was administered 
      in combination with clenbuterol in vivo to determine whether activation of mTOR 
      was involved in mediating the effects of clenbuterol. Clenbuterol administration 
      increased the phosphorylation status of PKB/Akt, S6 kinase 1/p70(s6k), and 
      eukaryotic initiation factor 4E binding protein 1/PHAS-1. Clenbuterol treatment 
      induced growth by 27-41% in normal rats and attenuated muscle loss during 
      hindlimb suspension by 10-20%. Rapamycin treatment resulted in a 37-97% 
      suppression of clenbuterol-induced growth and a 100% reduction of the 
      muscle-sparing effect. In contrast, rapamycin was unable to block the 
      muscle-sparing effects of clenbuterol after denervation. Clenbuterol was also 
      shown to suppress the expression of the MuRF1 and MAFbx transcripts in muscles 
      from normal, denervated, and hindlimb-suspended rats. These results demonstrate 
      that the effects of clenbuterol are mediated, in part, through the activation of 
      Akt and mTOR signaling pathways.
FAU - Kline, William O
AU  - Kline WO
AD  - Univ. of California, Davis, Section of Neurobiology, Physiology, and Behavior, 
      One Shields Ave., Davis, California 95616, USA.
FAU - Panaro, Frank J
AU  - Panaro FJ
FAU - Yang, Hayung
AU  - Yang H
FAU - Bodine, Sue C
AU  - Bodine SC
LA  - eng
PT  - Journal Article
DEP - 20061026
PL  - United States
TA  - J Appl Physiol (1985)
JT  - Journal of applied physiology (Bethesda, Md. : 1985)
JID - 8502536
RN  - 0 (Adrenergic beta-Agonists)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Muscle Proteins)
RN  - 0 (Tripartite Motif Proteins)
RN  - EC 2.3.2.27 (Fbxo32 protein, rat)
RN  - EC 2.3.2.27 (SKP Cullin F-Box Protein Ligases)
RN  - EC 2.3.2.27 (Trim63 protein, rat)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
RN  - XTZ6AXU7KN (Clenbuterol)
SB  - IM
MH  - Adrenergic beta-Agonists/*pharmacology
MH  - Animals
MH  - Clenbuterol/*pharmacology
MH  - Drug Interactions
MH  - Female
MH  - Hindlimb Suspension
MH  - Immunosuppressive Agents/*pharmacology
MH  - Muscle Proteins/metabolism
MH  - Muscle, Skeletal/drug effects/*growth & development
MH  - Muscular Atrophy/physiopathology/*prevention & control
MH  - Protein Kinases/physiology
MH  - Proto-Oncogene Proteins c-akt/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - SKP Cullin F-Box Protein Ligases/metabolism
MH  - Signal Transduction/physiology
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Tripartite Motif Proteins
MH  - Ubiquitin-Protein Ligases/metabolism
EDAT- 2006/10/28 09:00
MHDA- 2007/03/23 09:00
CRDT- 2006/10/28 09:00
PHST- 2006/10/28 09:00 [pubmed]
PHST- 2007/03/23 09:00 [medline]
PHST- 2006/10/28 09:00 [entrez]
AID - 00873.2006 [pii]
AID - 10.1152/japplphysiol.00873.2006 [doi]
PST - ppublish
SO  - J Appl Physiol (1985). 2007 Feb;102(2):740-7. doi: 
      10.1152/japplphysiol.00873.2006. Epub 2006 Oct 26.