Indomethacin preserves skeletal muscle mass and reduces biological markers of muscle degradation in mice with cancer cachexia

2.50
Hdl Handle:
http://hdl.handle.net/10755/161196
Type:
Presentation
Title:
Indomethacin preserves skeletal muscle mass and reduces biological markers of muscle degradation in mice with cancer cachexia
Abstract:
Indomethacin preserves skeletal muscle mass and reduces biological markers of muscle degradation in mice with cancer cachexia
Conference Sponsor:Midwest Nursing Research Society
Conference Year:2005
Author:McCarthy, Donna, PhD, RN
P.I. Institution Name:University of Wisconsin - Madison
Title:Professor
Contact Address:School of Nursing, 600 Highland Ave, Room K6-326, Madison, WI, 53792-2455, USA
Contact Telephone:608-263-2476
Skeletal muscle wasting is a prominent feature of cancer cachexia and
contributes significantly to the cancer patientÆs experience of weakness
and fatigue. The biology of muscle wasting involves decreased protein
synthesis and increased activity of the ubiquitin-proteasome pathway of
protein degradation. Interventions that reverse this process are needed.
Indomethacin has been shown to preserve skeletal muscle mass in animal
models of cancer cachexia though the mechanism of action is unknown. In
the present study, groups of 6 mice each, with and without tumors, were
given 1 or 5 mg/kg/day indomethacin in their food. Growth of the tumor was
associated with diminished gastrocnemius muscle mass. The muscles of the
tumor-bearing mice had increased levels of factors associated with muscle
fiber degradation: actin, ubiquitin-conjugated proteins, free ubiquitin,
E3 ubiquitin ligases and the type 1 receptor for tumor necrosis
factor-alpha (TNFR1). Tumor-bearing mice that were given 5 mg/kg/day, but
not 1 mg/kg/day indomethacin in their food for 21 days had reduced muscle
wasting and reduced levels of actin and the E3 ligases in their muscles.
Both 5 and 1 mg/kg/day indomethacin significantly reduced levels of TNFR1,
while neither dose affected levels of free ubiquitin. Paradoxically,
indomethacin increased levels of ubiquitin-conjugated proteins in the
muscles of both tumor-bearing and healthy control animals, suggesting it
may function as an inhibitor of proteasome activity. These data suggest
that the beneficial effects of indomethacin in this animal model of cancer
cachexia may involve inhibition of TNF and ubiquitin-mediated pathways of
skeletal muscle wasting. Further studies of the effects of
anti-inflammatory drugs in other animal models of cancer cachexia are
needed before undertaking clinical trials in cancer patients.
Repository Posting Date:
26-Oct-2011
Date of Publication:
17-Oct-2011
Sponsors:
Midwest Nursing Research Society

Full metadata record

DC FieldValue Language
dc.typePresentationen_GB
dc.titleIndomethacin preserves skeletal muscle mass and reduces biological markers of muscle degradation in mice with cancer cachexiaen_GB
dc.identifier.urihttp://hdl.handle.net/10755/161196-
dc.description.abstract<table><tr><td colspan="2" class="item-title">Indomethacin preserves skeletal muscle mass and reduces biological markers of muscle degradation in mice with cancer cachexia</td></tr><tr class="item-sponsor"><td class="label">Conference Sponsor:</td><td class="value">Midwest Nursing Research Society</td></tr><tr class="item-year"><td class="label">Conference Year:</td><td class="value">2005</td></tr><tr class="item-author"><td class="label">Author:</td><td class="value">McCarthy, Donna, PhD, RN</td></tr><tr class="item-institute"><td class="label">P.I. Institution Name:</td><td class="value">University of Wisconsin - Madison</td></tr><tr class="item-author-title"><td class="label">Title:</td><td class="value">Professor</td></tr><tr class="item-address"><td class="label">Contact Address:</td><td class="value">School of Nursing, 600 Highland Ave, Room K6-326, Madison, WI, 53792-2455, USA</td></tr><tr class="item-phone"><td class="label">Contact Telephone:</td><td class="value">608-263-2476</td></tr><tr class="item-email"><td class="label">Email:</td><td class="value">domccart@wisc.edu</td></tr><tr><td colspan="2" class="item-abstract">Skeletal muscle wasting is a prominent feature of cancer cachexia and <br/> contributes significantly to the cancer patient&AElig;s experience of weakness <br/> and fatigue. The biology of muscle wasting involves decreased protein <br/> synthesis and increased activity of the ubiquitin-proteasome pathway of <br/> protein degradation. Interventions that reverse this process are needed. <br/> Indomethacin has been shown to preserve skeletal muscle mass in animal <br/> models of cancer cachexia though the mechanism of action is unknown. In <br/> the present study, groups of 6 mice each, with and without tumors, were <br/> given 1 or 5 mg/kg/day indomethacin in their food. Growth of the tumor was <br/> associated with diminished gastrocnemius muscle mass. The muscles of the <br/> tumor-bearing mice had increased levels of factors associated with muscle <br/> fiber degradation: actin, ubiquitin-conjugated proteins, free ubiquitin, <br/> E3 ubiquitin ligases and the type 1 receptor for tumor necrosis <br/> factor-alpha (TNFR1). Tumor-bearing mice that were given 5 mg/kg/day, but <br/> not 1 mg/kg/day indomethacin in their food for 21 days had reduced muscle <br/> wasting and reduced levels of actin and the E3 ligases in their muscles. <br/> Both 5 and 1 mg/kg/day indomethacin significantly reduced levels of TNFR1, <br/> while neither dose affected levels of free ubiquitin. Paradoxically, <br/> indomethacin increased levels of ubiquitin-conjugated proteins in the <br/> muscles of both tumor-bearing and healthy control animals, suggesting it <br/> may function as an inhibitor of proteasome activity. These data suggest <br/> that the beneficial effects of indomethacin in this animal model of cancer <br/> cachexia may involve inhibition of TNF and ubiquitin-mediated pathways of <br/> skeletal muscle wasting. Further studies of the effects of <br/> anti-inflammatory drugs in other animal models of cancer cachexia are <br/> needed before undertaking clinical trials in cancer patients.</td></tr></table>en_GB
dc.date.available2011-10-26T23:17:27Z-
dc.date.issued2011-10-17en_GB
dc.date.accessioned2011-10-26T23:17:27Z-
dc.description.sponsorshipMidwest Nursing Research Societyen_GB
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