Mechanical ventilation induces alterations of the ubiquitin-proteasome pathway in the diaphragm
Prolonged mechanical ventilation (MV) results in diaphragmatic atrophy due, in part, to an increase in proteolysis. These experiments tested the hypothesis that MV-induced diaphragmatic proteolysis is accompanied by increased expression of key components of the ubiquitin-proteasome pathway (UPP). To...
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th-mahidol.163632018-06-21T15:29:03Z Mechanical ventilation induces alterations of the ubiquitin-proteasome pathway in the diaphragm Keith C. DeRuisseau Andreas N. Kavazis Melissa A. Deering Darin J. Falk Darin Van Gammeren Tossaporn Yimlamai George A. Ordway Scott K. Powers University of Florida Mahidol University UT Southwestern Medical School Biochemistry, Genetics and Molecular Biology Health Professions Medicine Prolonged mechanical ventilation (MV) results in diaphragmatic atrophy due, in part, to an increase in proteolysis. These experiments tested the hypothesis that MV-induced diaphragmatic proteolysis is accompanied by increased expression of key components of the ubiquitin-proteasome pathway (UPP). To test this postulate, we investigated the effect of prolonged MV on UPP components. and determined the trypsin-like and peptidylglutamyl peptide hydrolyzing activities of the 20S proteasome. Adult Sprague-Dawley rats were assigned to either control or 12-h MV groups (n = 7/group). MV animals were anesthetized, tracheostomized, and ventilated with room air for 12 h. Animals in the control group were acutely anesthetized but not exposed to MV. Compared with controls, MV animals demonstrated increased diaphragmatic mRNA levels of two ubiquitin ligases, muscle atrophy F-box (+8.3-fold) and muscle ring finger 1 (+19.0-fold). However, MV did not alter mRNA levels of 14-kDa ubiquitin-conjugating enzyme, polyubiquitin, proteasome-activating complex PA28, or 20S α-subunit 7. Protein levels of 14-kDa ubiquitin-conjugating enzyme and proteasome-activating complex PA28 were not altered following MV, but 20S α-subunit 7 levels declined (-17.7%). MV increased diaphragmatic trypsin-like activity (+31%) but did not alter peptidylglutamyl peptide hydrolyzing activity. Finally, compared with controls, MV increased ubiquitin-protein conjugates in both the myofibrillar (+24.9%) and cytosolic (+54.7%) fractions of the diaphragm. These results are consistent with the hypothesis that prolonged MV increases diaphragmatic levels of key components within the UPP and that increases in 20S proteasome activity contribute to MV-induced diaphragmatic proteolysis and atrophy. Copyright © 2005 the American Physiological Society. 2018-06-21T08:09:48Z 2018-06-21T08:09:48Z 2005-04-01 Article Journal of Applied Physiology. Vol.98, No.4 (2005), 1314-1321 10.1152/japplphysiol.00993.2004 87507587 2-s2.0-15444366596 https://repository.li.mahidol.ac.th/handle/123456789/16363 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=15444366596&origin=inward |
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Biochemistry, Genetics and Molecular Biology Health Professions Medicine Keith C. DeRuisseau Andreas N. Kavazis Melissa A. Deering Darin J. Falk Darin Van Gammeren Tossaporn Yimlamai George A. Ordway Scott K. Powers Mechanical ventilation induces alterations of the ubiquitin-proteasome pathway in the diaphragm |
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Prolonged mechanical ventilation (MV) results in diaphragmatic atrophy due, in part, to an increase in proteolysis. These experiments tested the hypothesis that MV-induced diaphragmatic proteolysis is accompanied by increased expression of key components of the ubiquitin-proteasome pathway (UPP). To test this postulate, we investigated the effect of prolonged MV on UPP components. and determined the trypsin-like and peptidylglutamyl peptide hydrolyzing activities of the 20S proteasome. Adult Sprague-Dawley rats were assigned to either control or 12-h MV groups (n = 7/group). MV animals were anesthetized, tracheostomized, and ventilated with room air for 12 h. Animals in the control group were acutely anesthetized but not exposed to MV. Compared with controls, MV animals demonstrated increased diaphragmatic mRNA levels of two ubiquitin ligases, muscle atrophy F-box (+8.3-fold) and muscle ring finger 1 (+19.0-fold). However, MV did not alter mRNA levels of 14-kDa ubiquitin-conjugating enzyme, polyubiquitin, proteasome-activating complex PA28, or 20S α-subunit 7. Protein levels of 14-kDa ubiquitin-conjugating enzyme and proteasome-activating complex PA28 were not altered following MV, but 20S α-subunit 7 levels declined (-17.7%). MV increased diaphragmatic trypsin-like activity (+31%) but did not alter peptidylglutamyl peptide hydrolyzing activity. Finally, compared with controls, MV increased ubiquitin-protein conjugates in both the myofibrillar (+24.9%) and cytosolic (+54.7%) fractions of the diaphragm. These results are consistent with the hypothesis that prolonged MV increases diaphragmatic levels of key components within the UPP and that increases in 20S proteasome activity contribute to MV-induced diaphragmatic proteolysis and atrophy. Copyright © 2005 the American Physiological Society. |
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University of Florida |
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University of Florida Keith C. DeRuisseau Andreas N. Kavazis Melissa A. Deering Darin J. Falk Darin Van Gammeren Tossaporn Yimlamai George A. Ordway Scott K. Powers |
format |
Article |
author |
Keith C. DeRuisseau Andreas N. Kavazis Melissa A. Deering Darin J. Falk Darin Van Gammeren Tossaporn Yimlamai George A. Ordway Scott K. Powers |
author_sort |
Keith C. DeRuisseau |
title |
Mechanical ventilation induces alterations of the ubiquitin-proteasome pathway in the diaphragm |
title_short |
Mechanical ventilation induces alterations of the ubiquitin-proteasome pathway in the diaphragm |
title_full |
Mechanical ventilation induces alterations of the ubiquitin-proteasome pathway in the diaphragm |
title_fullStr |
Mechanical ventilation induces alterations of the ubiquitin-proteasome pathway in the diaphragm |
title_full_unstemmed |
Mechanical ventilation induces alterations of the ubiquitin-proteasome pathway in the diaphragm |
title_sort |
mechanical ventilation induces alterations of the ubiquitin-proteasome pathway in the diaphragm |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/16363 |
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1763489197330530304 |