Document Detail

Mechanical ventilation-induced oxidative stress in the diaphragm: role of heme oxygenase-1.
MedLine Citation:
PMID:  21106654     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Prolonged mechanical ventilation (MV) results in a rapid onset of diaphragmatic atrophy that is primarily due to increased proteolysis. Although MV-induced protease activation can involve several factors, it is clear that oxidative stress is a required signal for protease activation in the diaphragm during prolonged MV. However, the oxidant-producing pathways in the diaphragm that contribute to MV-induced oxidative stress remain unknown. We have demonstrated that prolonged MV results in increased diaphragmatic expression of a key stress-sensitive enzyme, heme oxygenase (HO)-1. Paradoxically, HO-1 can function as either a pro-oxidant or an antioxidant, and the role that HO-1 plays in MV-induced diaphragmatic oxidative stress is unknown. We tested the hypothesis that HO-1 acts as a pro-oxidant in the diaphragm during prolonged MV.
METHODS: To determine whether HO-1 functions as a pro-oxidant or an antioxidant in the diaphragm during MV, we assigned rats into three experimental groups: (1) a control group, (2) a group that received 18 h of MV and saline solution, and (3) a group that received 18 h of MV and was treated with a selective HO-1 inhibitor. Indices of oxidative stress, protease activation, and fiber atrophy were measured in the diaphragm.
RESULTS: Inhibition of HO-1 activity did not prevent or exacerbate MV-induced diaphragmatic oxidative stress (as indicated by biomarkers of oxidative damage). Further, inhibition of HO-1 activity did not influence MV-induced protease activation or myofiber atrophy in the diaphragm.
CONCLUSIONS: Our results indicate that HO-1 is neither a pro-oxidant nor an antioxidant in the diaphragm during MV. Furthermore, our findings reveal that HO-1 does not play an important role in MV-induced protease activation and diaphragmatic atrophy.
Darin J Falk; Andreas N Kavazis; Melissa A Whidden; Ashley J Smuder; Joseph M McClung; Matthew B Hudson; Scott K Powers
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2010-11-24
Journal Detail:
Title:  Chest     Volume:  139     ISSN:  1931-3543     ISO Abbreviation:  Chest     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-06     Completed Date:  2011-06-07     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0231335     Medline TA:  Chest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  816-24     Citation Subset:  AIM; IM    
Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA.
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MeSH Terms
Blotting, Western
Diaphragm / metabolism*,  pathology
Disease Models, Animal
Follow-Up Studies
Heme Oxygenase-1 / antagonists & inhibitors,  metabolism*
Muscular Atrophy / etiology,  metabolism*,  pathology
Oxidative Stress / physiology*
Rats, Sprague-Dawley
Respiration, Artificial / adverse effects*
Time Factors
Grant Support
Reg. No./Substance:
EC Oxygenase-1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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