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

Abstract

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-alpha 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-kappaB, 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-alpha 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.

• Authors: Hans Degens, Anne K Swisher, Yvonne F Heijdra, Parco M Siu, P N Richard Dekhuijzen, Stephen E Alway
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 293 Issue 1 Pg. R135-44 (Jul 2007) ISSN: 0363-6119 [Print] United States
• PMID: 17395785 (Publication Type: Journal Article)

Chemical References

• Inhibitor of Differentiation Protein 2
• MyoD Protein
• NF-kappa B
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Caspase 3
• Myosin Heavy Chains

Topics

• Animals
• Apoptosis (physiology)
• Caspase 3 (metabolism)
• Cell Nucleus (metabolism)
• Cricetinae
• Cytosol (metabolism)
• DNA Fragmentation
• Diaphragm (metabolism, pathology)
• Emphysema (metabolism, pathology)
• Inhibitor of Differentiation Protein 2 (biosynthesis)
• Male
• Mesocricetus
• Muscle Fibers, Skeletal (chemistry, physiology)
• Muscle, Skeletal (metabolism, pathology)
• MyoD Protein (genetics)
• Myosin Heavy Chains (metabolism)
• NF-kappa B (biosynthesis)
• Pulmonary Disease, Chronic Obstructive (metabolism, pathology)
• RNA, Messenger (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (biosynthesis)