Changes in Ubiquitin Proteasome Pathway Gene Expression in Skeletal Muscle With Exercise and Statins.

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Sharon Hope - 31 Oct 2005 03:25 GMT

Arterioscler Thromb Vasc Biol. 2005 Oct 13;
http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3051&uid=16224050&db=p
ubmed&url=http://atvb.ahajournals.org/cgi/pmidlookup?view=reprint&pmid=16224050

Urso ML, Clarkson PM, Hittel D, Hoffman EP, Thompson PD.

Department of Exercise Science, University of Massachusetts, Amherst, Mass;
the Division of Cardiology, Henry Low Heart Center, Hartford Hospital,
Hartford, Conn; and the Research Center for Genetic Medicine, Children's
National Medical Center, Washington DC.

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.

PMID: 16224050 [PubMed - as supplied by publisher]

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William Wagner - 31 Oct 2005 12:00 GMT

> Arterioscler Thromb Vasc Biol. 2005 Oct 13;
> http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3051&uid=16224050&db
[quoted text clipped - 7 lines]
> Hartford, Conn; and the Research Center for Genetic Medicine, Children's
> National Medical Center, Washington DC.

> 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.
>
> PMID: 16224050 [PubMed - as supplied by publisher]

This is something that main street media should be aware of.

My experience suggests it takes a long time to occur and a long time
to heal. Almost like vitamin deficiency. My calfs went from 18 inches
to 14 over a four year period. So measure your muscle girth and
document it over time if you decide to take statins. To think we are
punished for heavy workout is outside the box !

I think we touched on this before here. Good to see it addressed in
Pub Med.

Thanks Sharon!

Bill

PS I think of muscular dystrophy.

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eml - 31 Oct 2005 15:29 GMT

Impairment of the ubiquitin-proteasome system has been implicated in
neurodegenerative disease, also--it is the primary mechanism of disese
uncovered in inherited form of parkinson's involving the Parkin gene
(Park2) which accounts for most of the inherited forms of Parkinson;'s
thus far discovered:

Klein, C. (2001). "[The genetics of Parkinson syndrome]." Schweiz
Rundsch Med Prax 90(23): 1015-23.
A genetic contribution to the etiology of Parkinson's disease was first
suspected by Charcot and later confirmed by case control, family, and
twin studies, as well as by the description of large parkinsonian
families with Mendelian inheritance of the disease. Recent progress in
the field of molecular neurogenetics has led to the identification of
several Parkinson disease genes and gene loci. Mutations in the
alpha-Synuclein gene (PARK1) and in the gene for the ubiquitin
C-terminal hydrolase I (PARK5), along with two gene loci harboring
currently unknown genes (PARK3 and PARK4), have been linked to very
rare autosomal dominantly inherited parkinsonian syndromes. Mutations
in the parkins gene (PARK2), causing autosomal recessive early-onset
parkinsonism, are much more common and therefore of clinical relevance.
A second gene locus for an autosomal dominantly inherited Parkinsonian
syndrome was recently localized on chromosome 1 (PARK6). All three
parkinson genes identified thus far imply the involvement of the
ubiquitin pathway of protein degradation in the pathogenesis of
Parkinson's disease.

thanks sharon for finding and posting the abstract relating statins to
interruption to the UPS. There are many other published studies and
articles discussing the ubiquitin-proteasome system and its dysfunction
in parkinson's. m

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