Klotho and smoking - An interplay influencing the skeletal muscle function deficits that occur in COPD
| Autor: | Michael I. Polkey, Y.M. Andersson, Sonya Jackson, Nicholas Hart, Nicholas S Hopkinson, Anna Donaldson, Amy Lewis, Piet L.B. Bruijnzeel, Brian Bolognese, Joseph P. Foley, Mehul S. Patel, Jy Lee, Patricia L. Podolin, GS Haji, Paul R. Kemp, William D.-C. Man, Samantha A. Natanek |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Fibroblast growth factor 23 Spirometry medicine.medical_specialty Respiratory System 030204 cardiovascular system & hematology urologic and male genital diseases 1102 Cardiovascular Medicine And Haematology Klotho smoking Quadriceps Muscle Mice Pulmonary Disease Chronic Obstructive 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Humans COPD skeletal muscle Muscle Skeletal Klotho Proteins Wasting Glucuronidase medicine.diagnostic_test business.industry Smoking Skeletal muscle 1103 Clinical Sciences medicine.disease Immunohistochemistry female genital diseases and pregnancy complications Mice Inbred C57BL medicine.anatomical_structure Endocrinology 030228 respiratory system Ageing regeneration Regression Analysis Female medicine.symptom business Hormone |
| Zdroj: | Patel, M S, Donaldson, A V, Lewis, A, Natanek, S A, Lee, J Y, Andersson, Y M, Haji, G, Jackson, S G, Bolognese, B J, Foley, J P, Podolin, P L, Bruijnzeel, P L B, Hart, N, Hopkinson, N S, D-C Man, W, Kemp, P R & Polkey, M I 2016, ' Klotho and smoking-An interplay influencing the skeletal muscle function deficits that occur in COPD ', Respiratory Medicine . https://doi.org/10.1016/j.rmed.2016.02.004 |
| Popis: | Background Klotho is an ‘anti-ageing' hormone and transmembrane protein; Klotho deficient mice develop a similar ageing phenotype to smokers including emphysema and muscle wasting. The objective of this study was to evaluate skeletal muscle and circulating Klotho protein in smokers and COPD patients and to relate Klotho levels to relevant skeletal muscle parameters. We sought to validate our findings by undertaking complimentary murine studies. Methods Fat free mass, quadriceps strength and spirometry were measured in 87 participants (61 COPD, 13 ‘healthy smokers' and 13 never smoking controls) in whom serum and quadriceps Klotho protein levels were also measured. Immunohistochemistry was performed to demonstrate the location of Klotho protein in human skeletal muscle and in mouse skeletal muscle in which regeneration was occurring following injury induced by electroporation. In a separate study, gastrocnemius Klotho protein was measured in mice exposed to 77 weeks of smoke or sham air. Results Quadriceps Klotho levels were lower in those currently smoking (p = 0.01), irrespective of spirometry, but were not lower in patients with COPD. A regression analysis identified current smoking status as the only independent variable associated with human quadriceps Klotho levels, an observation supported by the finding that smoke exposed mice had lower gastrocnemius Klotho levels than sham exposed mice (p = 0.005). Quadriceps Klotho levels related to local oxidative stress but were paradoxically higher in patients with established muscle wasting or weakness; the unexpected relationship with low fat free mass was the only independent association. Within locomotor muscle, Klotho localized to the plasma membrane and to centralized nuclei in humans and in mice with induced muscle damage. Serum Klotho had an independent association with quadriceps strength but did not relate to quadriceps Klotho levels or to spirometric parameters. Conclusions Klotho is expressed in skeletal muscle and levels are reduced by smoking. Despite this, quadriceps Klotho protein expression in those with established disease appears complex as levels were paradoxically elevated in COPD patients with established muscle wasting. Whilst serum Klotho levels were not reduced in smokers or COPD patients and were not associated with quadriceps Klotho protein, they did relate to quadriceps strength. |
| Databáze: | OpenAIRE |
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