Mechanical ventilation induces alterations of the ubiquitin-proteasome pathway in the diaphragm
| Autor: | Keith C. DeRuisseau, G. A. Ordway, Darin J. Falk, Tossaporn Yimlamai, Andreas N. Kavazis, Scott K. Powers, Melissa A. Deering, Darin Van Gammeren |
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| Rok vydání: | 2005 |
| Předmět: |
Proteasome Endopeptidase Complex
Physiology medicine.medical_treatment Proteolysis Diaphragm Diaphragmatic breathing Biology Rats Sprague-Dawley Atrophy Ubiquitin Physiology (medical) Respiratory muscle medicine Animals Mechanical ventilation medicine.diagnostic_test medicine.disease Adaptation Physiological Respiration Artificial Rats Diaphragm (structural system) Cell biology Gene Expression Regulation Proteasome Biochemistry biology.protein Female Signal Transduction |
| Zdroj: | Journal of Applied Physiology. 98:1314-1321 |
| ISSN: | 1522-1601 8750-7587 |
| DOI: | 10.1152/japplphysiol.00993.2004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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