Chapter

Neurobiology of Respiration

Volume 788 of the series Advances in Experimental Medicine and Biology pp 7-17

Date:

Involvement of NF-κB and Muscle Specific E3 Ubiquitin Ligase MuRF1 in Cigarette Smoke-Induced Catabolism in C2 Myotubes

  • Sharon KaisariAffiliated withDepartment of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion – Israel Institute of Technology
  • , Oren RomAffiliated withDepartment of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion – Israel Institute of Technology
  • , Dror AizenbudAffiliated withDepartment of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion – Israel Institute of TechnologyOrthodontic and Craniofacial Department, Rambam Health Care Campus
  • , Abraham Z. ReznickAffiliated withDepartment of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion – Israel Institute of Technology Email author 

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Cigarette smoking has been identified as a risk factor for muscular damage and sarcopenia, the age-related loss of muscle mass and strength in old age. Cigarette smoke (CS)-induced oxidative stress and p38 MAPK activation have been shown to be the main cellular mechanisms leading to skeletal muscle catabolism. In order to investigate the involvement of NF-κB as another possible cellular mechanism by which CS promotes muscle catabolism, C2 myotubes, from an in vitro skeletal muscle cell line, were exposed to different time periods of whole vapor phase CS in the presence or absence of NF-κB inhibitor, IMD-0354. The CS-induced reduction in diameter of myotubes and time-dependent degradation of the main contractile protein myosin heavy chain were abolished by NF-κB inhibition. Also, C2 exposure to CS resulted in IκB-α degradation and NF-κB activation, which led to upregulation of the muscle specific E3 ubiquitin ligase MuRF1, but not MAFbx/atrogin-1. In conclusion, our results demonstrate that vapor phase CS exposure to skeletal myotubes triggers NF-κB activation leading to skeletal muscle cell damage and breakdown of muscle proteins mediated by muscle specific E3 ubiquitin ligase MuRF1. Our findings provide another possible molecular mechanism for the catabolic effects of CS in skeletal muscle.

Keywords

Cigarette smoke E3 ubiquitin ligases NF-κB Muscle atrophy Protein degradation p38 MAPK