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Changes in ubiquitin proteasome pathway gene expression in skeletal muscle with exercise and statins.
Arterioscler Thromb Vasc Biol. 2005 Dec; 25(12):2560-6.AT

Abstract

OBJECTIVE

Statins are safe medications but have side effects including myalgia and rhabdomyolysis. How statins provoke muscle damage is not known, but this effect is exacerbated by exercise.

METHODS AND RESULTS

Healthy subjects took Atorvastatin (80 mg/daily) or placebo for 4 weeks. Biopsies of both vastus lateralis muscles were performed 8 hours after eccentric exercise (known to result in muscle soreness and damage) of the left leg at baseline and the right leg after statin/placebo treatment. Gene expression was determined using Affymetrix GeneChips, and selected genes confirmed by polymerase chain reaction (qRT-PCR). Atorvastatin had little effect on gene expression at rest. When combined with exercise, 56 genes were differentially expressed with 18% involved in the ubiquitin proteasome pathway (UPP) and 20% involved in protein folding and catabolism, and apoptosis.

CONCLUSIONS

This is the first investigation to our knowledge to implicate involvement of the UPP in skeletal muscle in response to combined exercise and statin treatment, possibly explaining the onset of myalgia with exertion. Statins may alter the response of muscle to exercise stress by altering the action of the UPP, protein folding, and catabolism, disrupting the balance between protein degradation and repair.

Authors+Show Affiliations

Department of Exercise Science, University of Massachusetts, Amherst, MA 01003, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Controlled Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16224050

Citation

Urso, Maria L., et al. "Changes in Ubiquitin Proteasome Pathway Gene Expression in Skeletal Muscle With Exercise and Statins." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 12, 2005, pp. 2560-6.
Urso ML, Clarkson PM, Hittel D, et al. Changes in ubiquitin proteasome pathway gene expression in skeletal muscle with exercise and statins. Arterioscler Thromb Vasc Biol. 2005;25(12):2560-6.
Urso, M. L., Clarkson, P. M., Hittel, D., Hoffman, E. P., & Thompson, P. D. (2005). Changes in ubiquitin proteasome pathway gene expression in skeletal muscle with exercise and statins. Arteriosclerosis, Thrombosis, and Vascular Biology, 25(12), 2560-6.
Urso ML, et al. Changes in Ubiquitin Proteasome Pathway Gene Expression in Skeletal Muscle With Exercise and Statins. Arterioscler Thromb Vasc Biol. 2005;25(12):2560-6. PubMed PMID: 16224050.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in ubiquitin proteasome pathway gene expression in skeletal muscle with exercise and statins. AU - Urso,Maria L, AU - Clarkson,Priscilla M, AU - Hittel,Dustin, AU - Hoffman,Eric P, AU - Thompson,Paul D, Y1 - 2005/10/13/ PY - 2005/10/15/pubmed PY - 2006/1/21/medline PY - 2005/10/15/entrez SP - 2560 EP - 6 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler Thromb Vasc Biol VL - 25 IS - 12 N2 - OBJECTIVE: Statins are safe medications but have side effects including myalgia and rhabdomyolysis. How statins provoke muscle damage is not known, but this effect is exacerbated by exercise. METHODS AND RESULTS: Healthy subjects took Atorvastatin (80 mg/daily) or placebo for 4 weeks. Biopsies of both vastus lateralis muscles were performed 8 hours after eccentric exercise (known to result in muscle soreness and damage) of the left leg at baseline and the right leg after statin/placebo treatment. Gene expression was determined using Affymetrix GeneChips, and selected genes confirmed by polymerase chain reaction (qRT-PCR). Atorvastatin had little effect on gene expression at rest. When combined with exercise, 56 genes were differentially expressed with 18% involved in the ubiquitin proteasome pathway (UPP) and 20% involved in protein folding and catabolism, and apoptosis. CONCLUSIONS: This is the first investigation to our knowledge to implicate involvement of the UPP in skeletal muscle in response to combined exercise and statin treatment, possibly explaining the onset of myalgia with exertion. Statins may alter the response of muscle to exercise stress by altering the action of the UPP, protein folding, and catabolism, disrupting the balance between protein degradation and repair. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/16224050/Changes_in_ubiquitin_proteasome_pathway_gene_expression_in_skeletal_muscle_with_exercise_and_statins_ L2 - https://www.ahajournals.org/doi/10.1161/01.ATV.0000190608.28704.71?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -