title: Lack of caspase-3 attenuates immobilization-induced muscle atrophy and loss of tension generation along with mitigation of apoptosis and inflammation.
abstract: BACKGROUND
  Immobilization by casting induces disuse muscle atrophy (DMA).
  
  
  METHODS
  Using wild type (WT) and caspase-3 knockout (KO) mice, we evaluated the effect of caspase-3 on muscle mass, apoptosis, and inflammation during DMA.
  
  
  RESULTS
  Caspase-3 deficiency significantly attenuated muscle mass decrease [gastrocnemius: 28 ± 1% in KO vs. 41 ± 3% in WT; soleus: 47 ± 2% in KO vs. 56 ± 2% in WT; (P < 0.05)] and gastrocnemius twitch tension decrease (23 ± 4% in KO vs. 36 ± 3% in WT, P < 0.05) at day 14 in immobilized vs. contralateral hindlimb. Lack of caspase-3 decreased immobilization-induced increased apoptotic myonuclei (3.2-fold) and macrophage infiltration (2.2-fold) in soleus muscle and attenuated increased monocyte chemoattractant protein-1 mRNA expression (2-fold in KO vs. 18-fold in WT) in gastrocnemius.
  
  
  CONCLUSIONS
  Caspase-3 plays a key role in DMA and associated decreased tension, presumably by acting on the apoptosis and inflammation pathways.
authors: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Room 206, 5l Blossom Street, Boston, Massachusetts 02114, USA.
authors: Shimei
authors: S
authors: Zhu
authors: Michio
authors: M
authors: Nagashima
authors: Mohammed A S
authors: MA
authors: Khan
authors: Shingo
authors: S
authors: Yasuhara
authors: Masao
authors: M
authors: Kaneki
authors: J A Jeevendra
authors: JA
authors: Martyn
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D007103:Immobilization; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018932:Chemokine CCL2; D053148:Caspase 3
references: J Physiol. 2005 May 15;565(Pt 1):309-23
references: 15774533
references: J Biol Chem. 1993 May 5;268(13):9661-6
references: 8486654
references: J Neurochem. 2000 Feb;74(2):740-53
references: 10646526
references: Clin Chest Med. 2007 Sep;28(3):537-52, vi
references: 17720042
references: Biochim Biophys Acta. 2008 Dec;1782(12):730-43
references: 18992328
references: J Appl Physiol (1985). 2009 Jul;107(1):224-34
references: 19390003
references: Crit Care Med. 2008 Mar;36(3):910-6
references: 18431280
references: J Exp Med. 1989 Apr 1;169(4):1449-59
references: 2926329
references: Exp Gerontol. 2006 Mar;41(3):320-7
references: 16457979
references: Physiol Genomics. 2008 Sep 17;35(1):86-95
references: 18593863
references: Int J Sports Med. 2006 Feb;27(2):94-9
references: 16475053
references: Dev Biol. 2008 Dec 15;324(2):226-35
references: 18948093
references: Sports Med. 2008;38(11):947-69
references: 18937524
references: Am J Physiol Cell Physiol. 2007 May;292(5):C1723-31
references: 17182728
references: Muscle Nerve. 2006 Feb;33(2):155-65
references: 16228971
references: Intensive Care Med. 2008 Mar;34(3):561-7
references: 17952407
references: Am J Physiol Endocrinol Metab. 2000 Dec;279(6):E1235-41
references: 11093909
references: J Biol Chem. 2010 Jul 9;285(28):21249-57
references: 20424172
references: Surgery. 1999 Oct;126(4):744-9; discussion 749-50
references: 10520924
references: J Anat. 1989 Apr;163:1-5
references: 2558097
references: J Appl Physiol Respir Environ Exerc Physiol. 1982 May;52(5):1113-8
references: 7047468
references: Am J Physiol Endocrinol Metab. 2008 Nov;295(5):E1181-90
references: 18812460
references: J Exp Med. 1985 Mar 1;161(3):475-89
references: 3973536
references: J Biol Chem. 2001 Dec 28;276(52):49077-82
references: 11602613
references: J Am Coll Surg. 1995 Feb;180(2):161-70
references: 7850049
references: Circ Res. 2006 May 12;98(9):1177-85
references: 16574901
references: J Physiol. 2011 Feb 1;589(Pt 3):511-24
references: 21115641
references: J Muscle Res Cell Motil. 2002;23(1):65-9
references: 12363287
references: Cell Tissue Res. 2000 Nov;302(2):235-41
references: 11131134
references: J Physiol. 1977 Jan;264(1):267-82
references: 839454
references: J Cereb Blood Flow Metab. 1998 Mar;18(3):238-47
references: 9498840
references: Curr Opin Clin Nutr Metab Care. 2005 May;8(3):271-5
references: 15809529
references: Genes Dev. 1998 Mar 15;12(6):806-19
references: 9512515
references: Science. 2001 Nov 23;294(5547):1704-8
references: 11679633
references: J Clin Invest. 2004 Jan;113(1):115-23
references: 14702115
references: J Appl Physiol Respir Environ Exerc Physiol. 1982 Aug;53(2):335-45
references: 7118655
references: Crit Care Med. 1999 Feb;27(2):275-85
references: 10075050
references: J Cereb Blood Flow Metab. 2004 Apr;24(4):419-31
references: 15087711
references: Oncogene. 1998 Dec 24;17(25):3237-45
references: 9916986
references: J Exp Med. 1989 Apr 1;169(4):1485-90
references: 2926331
references: J Immunol. 1998 Apr 1;160(7):3480-6
references: 9531309
references: Scand J Rehabil Med. 1980;12(1):27-31
references: 7384763
references: J Appl Physiol (1985). 2006 Jun;100(6):1770-7
references: 16484358
references: Int J Biochem Cell Biol. 2009 May;41(5):998-1001
references: 18761421