Background: Chronic obstructive pulmonary disease (COPD) is associated with an increased load on the diaphragm. Increased (eccentric) loading has been shown to result in disturbances in the cytoskeleton.
Objectives: We hypothesized that due to a continuous overload of the diaphragm in COPD patients, distinct alterations in the membrane-associated cytoskeleton occur, especially in the costameres.
Methods: Diaphragm biopsies from 7 COPD patients (forced expiratory volume in 1 s 62 +/- 3% predicted) and 5 non-COPD patients (forced expiratory volume in 1 s 105 +/- 6% predicted) were obtained. Cryosections of these biopsies were stained with antibodies against the costameric proteins of the focal adhesion complex (vinculin, talin and integrin-beta(1)), the dystroglycan complex (dystrophin and beta-dystroglycan) and the spectrin-based membrane cytoskeleton (beta-spectrin). Furthermore, in these cryosections, the basal membrane protein laminin was stained.
Results: We found no differences in the distribution and staining intensity of the costameric proteins of the focal adhesion complex, the dystroglycan complex and the spectrin-based membrane cytoskeleton in the diaphragm between the COPD and the non-COPD patients. Furthermore, no differences were observed in the expression of laminin in the diaphragm between COPD and non-COPD patients.
Conclusions: These results indicate that the increased loading to which the diaphragm is exposed in COPD does not result in disturbances in expression of the costameric system and histological damage of the sarcolemma.
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http://dx.doi.org/10.1159/000091270 | DOI Listing |
J Mol Cell Cardiol
January 2025
Shu Chien-Gene Lay Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Institute of Engineering Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92093, USA. Electronic address:
Vinculin (VCL) is a key adapter protein located in force-bearing costamere complexes, which mechanically couples the sarcomere to the ECM. Heterozygous vinculin frameshift genetic variants can contribute to cardiomyopathy when external stress is applied, but the mechanosensitive pathways underpinning VCL haploinsufficiency remain elusive. Here, we show that in response to extracellular matrix stiffening, heterozygous loss of VCL disrupts force-mediated costamere protein recruitment, thereby impairing cardiomyocyte contractility and sarcomere organization.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
November 2024
Laboratorio de Señalización Celular y Nanobiología, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
NPJ Microgravity
June 2024
Department of Biomedical Sciences, University of Padova, 35131, Padua, Italy.
Skeletal muscle undergoes atrophy and loss of force during long space missions, when astronauts are persistently exposed to altered gravity and increased ionizing radiation. We previously carried out mass spectrometry-based proteomics from skeletal muscle biopsies of two astronauts, taken before and after a mission on the International Space Station. The experiments were part of an effort to find similarities between spaceflight and bed rest, a ground-based model of unloading, focused on proteins located at the costameres.
View Article and Find Full Text PDFCirculation
April 2024
Center for Genetic Medicine, The Fourth Affiliated Hospital (C.X., G.Z., X.W., X.H., J.Z., S.H., R.X., F.H., P.H.), Zhejiang University School of Medicine, Hangzhou, China.
Background: Cardiac transverse tubules (T-tubules) are anchored to sarcomeric Z-discs by costameres to establish a regular spaced pattern. One of the major components of costameres is the dystrophin-glycoprotein complex (DGC). Nevertheless, how the assembly of the DGC coordinates with the formation and maintenance of T-tubules under physiological and pathological conditions remains unclear.
View Article and Find Full Text PDFJ Genet
February 2023
Department of Zoology, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, India.
Duchenne muscular dystrophy (DMD) is the most common form of progressive childhood muscular dystrophy associated with weakness of limbs, loss of ambulation, heart weakness and early death. The mutations causing either loss-of-expression or function of the full-length protein dystrophin (Dp427) from the gene are responsible for the disease pathology. Dp427 forms a part of the large dystroglycan complex, called DAPC, in the sarcolemma, and its absence derails muscle contraction.
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