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INFLAMMATION AND CYTOKINES

Apoptosis and Id2 expression in diaphragm and soleus muscle from the emphysematous hamster

¹Institute for Biophysical and Clinical Research into Human Movement, Manchester Metropolitan University, Alsager Campus, Cheshire, United Kingdom; ²Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; ³Laboratory of Muscle Biology and Sarcopenia, Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia; ⁴Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong

Submitted 22 January 2007 ; accepted in final form 23 March 2007

During chronic obstructive pulmonary disease (COPD) diaphragm and peripheral muscle weakness occur. Muscle remodeling and wasting may be a result of apoptosis and changes in muscle-specific transcription factors, such as MyoD, altering muscle-specific gene transcription and muscle regenerative capacity. To investigate this, we instilled under ketamine/xylazine anesthesia porcine elastase in the lungs of hamsters to induce emphysema. The emphysematous hamster is an accepted model for COPD. In the diaphragm and peripheral muscles we assessed the occurrence of apoptosis, and in the diaphragm and soleus also the expression of MyoD and inhibitor of differentiation protein 2 (Id2). There was no significant muscle atrophy in emphysematous hamsters. The mRNA levels of TNF- and markers of apoptosis were significantly elevated in the diaphragm and soleus muscles during emphysema. This was accompanied by an increased presence of nucleosomes in the cytosol. Caspase 3 activity and the DNA-binding activity of the p65 subunit of NF-B, however, were unaltered in all muscles. The protein expression of MyoD and Id2 were decreased and increased in the diaphragm and the soleus muscle, respectively. Thus, despite the absence of muscle atrophy in emphysematous hamsters, there was evidence of increased TNF- expression, apoptosis, and altered muscle-specific transcriptional regulation as reflected by decreased MyoD and elevated Id2 levels at least in the soleus and diaphragm muscle. These alterations may impair the regenerative capacity of skeletal muscles and ultimately contribute to muscle wasting.

apoptosis inducing factor; BAX; inhibitor of differentiation; MyoD; nuclear factor-B

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