Imperial College London
Alternate

DrPaulKemp

Faculty of Medicine, National Heart & Lung Institute

Reader in the Molecular Biology of Muscles
 
 
 
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Contact

 

+44 (0)20 7594 1716p.kemp

 
 
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Location

 

115Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Patel:2016:10.1016/j.rmed.2016.02.004,
author = {Patel, MS and Donaldson, AV and Lewis, A and Natanek, SA and Lee, JY and Andersson, YM and Haji, G and Jackson, SG and Bolognese, BJ and Foley, JP and Podolin, PL and Bruijnzeel, PLB and Hart, N and Hopkinson, NS and Man, WD-C and Kemp, PR and Polkey, MI},
doi = {10.1016/j.rmed.2016.02.004},
journal = {Respiratory Medicine},
pages = {50--56},
title = {Klotho and smoking – An interplay influencing the skeletal muscle function deficits that occur in COPD},
url = {http://dx.doi.org/10.1016/j.rmed.2016.02.004},
volume = {113},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundKlotho 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.MethodsFat 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.ResultsQuadriceps 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.ConclusionsKlotho is expressed
AU  - Patel,MS
AU  - Donaldson,AV
AU  - Lewis,A
AU  - Natanek,SA
AU  - Lee,JY
AU  - Andersson,YM
AU  - Haji,G
AU  - Jackson,SG
AU  - Bolognese,BJ
AU  - Foley,JP
AU  - Podolin,PL
AU  - Bruijnzeel,PLB
AU  - Hart,N
AU  - Hopkinson,NS
AU  - Man,WD-C
AU  - Kemp,PR
AU  - Polkey,MI
DO  - 10.1016/j.rmed.2016.02.004
EP  - 56
PY  - 2016///
SN  - 0954-6111
SP  - 50
TI  - Klotho and smoking – An interplay influencing the skeletal muscle function deficits that occur in COPD
T2  - Respiratory Medicine
UR  - http://dx.doi.org/10.1016/j.rmed.2016.02.004
UR  - http://hdl.handle.net/10044/1/30282
VL  - 113
ER  -
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