Lack of caspase-3 attenuates immobilization-induced muscle atrophy and loss of tension generation along with mitigation of apoptosis and inflammation

Authors

  • Shimei Zhu PhD,

    1. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Boston, Massachusetts, USA
    2. Harvard Medical School, Boston, Massachusetts, USA
    Search for more papers by this author
  • Michio Nagashima MD,

    1. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Boston, Massachusetts, USA
    2. Harvard Medical School, Boston, Massachusetts, USA
    Search for more papers by this author
  • Mohammed A.S. Khan PhD,

    1. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Boston, Massachusetts, USA
    2. Harvard Medical School, Boston, Massachusetts, USA
    Search for more papers by this author
  • Shingo Yasuhara MD, PhD,

    1. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Boston, Massachusetts, USA
    2. Harvard Medical School, Boston, Massachusetts, USA
    Search for more papers by this author
  • Masao Kaneki MD, PhD,

    1. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Boston, Massachusetts, USA
    2. Harvard Medical School, Boston, Massachusetts, USA
    Search for more papers by this author
  • J.A. Jeevendra Martyn MD, FCCM

    Corresponding author
    1. Harvard Medical School, Boston, Massachusetts, USA
    • Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Boston, Massachusetts, USA
    Search for more papers by this author

Correspondence to: J.A. Jeevendra Martyn; e-mail: jmartyn@partners.org

Abstract

Introduction: 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. Muscle Nerve 47: 711–721, 2013

Ancillary