Document Detail

Mitochondrial reactive oxygen species are required for hypoxia-induced degradation of keratin intermediate filaments.
MedLine Citation:
PMID:  19897662     Owner:  NLM     Status:  MEDLINE    
Hypoxia can cause stress and structural changes to the epithelial cytoskeleton. The intermediate filament (IF) network is known to reorganize in response to stress. We examined whether rats exposed to hypoxia had altered keratin IF expression in their alveolar epithelial type II (ATII) cells. There was a significant decrease in keratin protein levels in hypoxic ATII cells compared with those in ATII cells isolated from normoxic rats. To define the mechanisms regulating this process we studied changes to the keratin IF network in A549 cells (an alveolar epithelial cell line) exposed to 1.5% oxygen. We observed a time-dependent disassembly-degradation of keratin 8 and 18 proteins, which was associated with an increase in reactive oxygen species (ROS). Hypoxia-treated A549 cells deficient in mitochondrial DNA or A549 cells treated with a small interfering RNA against the Rieske iron-sulfur protein of mitochondrial complex III did not have increased levels of ROS nor was the keratin IF network disassembled and degraded. The superoxide dismutase (SOD)/catalase mimetic (EUK-134) prevented the hypoxia-mediated keratin IF degradation as did the overexpression of SOD1 but not of SOD2. Accordingly, we provide evidence that hypoxia promotes the disassembly and degradation of the keratin IF network via mitochondrial complex III-generated reactive oxygen species.-Na, N., Chandel, N. S., Litvan, J., Ridge, K. M. Mitochondrial reactive oxygen species are required for hypoxia-induced degradation of keratin intermediate filaments.
Ni Na; Navdeep S Chandel; Juan Litvan; Karen M Ridge
Publication Detail:
Type:  Journal Article     Date:  2009-11-06
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  24     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-02     Completed Date:  2010-05-11     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  799-809     Citation Subset:  IM    
Northwestern University Medical School, Pulmonary and Critical Care Medicine, 240 East Huron, McGaw 2328, Chicago, IL 60611, USA.
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MeSH Terms
Cell Hypoxia / physiology*
Cell Line, Tumor
Electrophoresis, Polyacrylamide Gel
Epithelial Cells / metabolism
Fluorescent Antibody Technique
Intermediate Filaments / metabolism*
Keratins / metabolism*
Mitochondria / metabolism*
Pulmonary Alveoli / cytology
RNA Interference
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism*
Reg. No./Substance:
0/Reactive Oxygen Species; 68238-35-7/Keratins

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