Back to Search
Start Over
Titin and diaphragm dysfunction in chronic obstructive pulmonary disease
- Source :
- American Journal of Respiratory and Critical Care Medicine, 173, 5, pp. 527-34, American Journal of Respiratory and Critical Care Medicine, 173(5), 527-534. American Thoracic Society, American Journal of Respiratory and Critical Care Medicine, 173, 527-34, Ottenheijm, C A C, Heunks, L M A, Hafmans, T, Van Der Ven, P F M, Benoist, C, Zhou, H, Labeit, S, Granzier, H L & Dekhuijzen, P N R 2006, ' Titin and diaphragm dysfunction in chronic obstructive pulmonary disease ', American Journal of Respiratory and Critical Care Medicine, vol. 173, no. 5, pp. 527-534 . https://doi.org/10.1164/rccm.200507-1056OC
- Publication Year :
- 2006
-
Abstract
- Contains fulltext : 34465.pdf (Publisher’s version ) (Closed access) RATIONALE: Recently, we have shown that Ca2+-activated force generation in diaphragm single fibers is impaired in patients with mild to moderate chronic obstructive pulmonary disease (COPD). For optimal active-force generation, the passive elasticity provided by titin is indispensable. OBJECTIVES: In the present study, we determined the passive-tension-length relations of single fibers of patients with mild to moderate COPD, hypothesizing that passive-elastic properties of diaphragm fibers are compromised. METHODS: Passive-tension-length relations were determined in diaphragm fibers from patients with and without COPD (predicted mean FEV1, 76 and 102%, respectively). In diaphragm homogenates titin expression was studied at the protein level by gel electrophoresis and at the transcript level by using a novel titin exon microarray. RESULTS: Diaphragm fibers from patients with COPD generate less passive tension on stretch. Titin content in the diaphragm did not differ between patients with and without COPD. However, titin exon transcript studies revealed up-regulation of seven exons, which code for spring elements in the elastic segment rich in proline, glutamate, valine, and lysine. Immunofluorescence analysis indicated elevated protein expression of the up-regulated splice variant in the COPD diaphragm. Simulation studies on titin molecules including the amino acids encoded by the seven up-regulated exons predicted reduced passive-tension generation on molecule stretch. CONCLUSIONS: Passive-tension generation of diaphragm single fibers is reduced in patients with COPD. Our results suggest that alternative splicing of the titin gene, resulting in increased length of the elastic segment rich in proline, glutamate, valine, and lysine, is involved. Interestingly, these changes occur already in patients with mild to moderate COPD.
- Subjects :
- Pulmonary and Respiratory Medicine
Adult
Male
medicine.medical_specialty
Pathology
Resuscitation
Diaphragm
Pulmonary disease
C. Chronic Obstructive Pulmonary Disease
Muscle Proteins
In Vitro Techniques
Critical Care and Intensive Care Medicine
Pulmonary Disease, Chronic Obstructive
Internal medicine
Intensive care
medicine
Humans
In patient
Connectin
Heart, lung and circulation [UMCN 2.1]
Molecular Biology
COPD
biology
business.industry
Respiratory disease
medicine.disease
musculoskeletal system
Pathogenesis and modulation of inflammation [N4i 1]
biology.protein
Cardiology
Titin
Female
Microbial pathogenesis and host defense [UMCN 4.1]
medicine.symptom
business
Protein Kinases
Muscle contraction
Muscle Contraction
Subjects
Details
- Language :
- English
- ISSN :
- 1073449X
- Volume :
- 173
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory and Critical Care Medicine
- Accession number :
- edsair.doi.dedup.....f6e6120624589d0a48f066ffae9f0aba