Hypoxia-mediated degradation of Na,K-ATPase via mitochondrial reactive oxygen species and the ubiquitin-conjugating system

Alejandro P Comellas; Laura A Dada; Emilia Lecuona; Liuska M Pesce; Navdeep S Chandel; Nancy Quesada; G R Scott Budinger; Ger J Strous; Aaron Ciechanover; Jacob I Sznajder

doi:10.1161/01.RES.0000222418.99976.1d

Back

Hypoxia-mediated degradation of Na,K-ATPase via mitochondrial reactive oxygen species and the ubiquitin-conjugating system

Journal article

Open access

Peer reviewed

Hypoxia-mediated degradation of Na,K-ATPase via mitochondrial reactive oxygen species and the ubiquitin-conjugating system

Alejandro P Comellas, Laura A Dada, Emilia Lecuona, Liuska M Pesce, Navdeep S Chandel, Nancy Quesada, G R Scott Budinger, Ger J Strous, Aaron Ciechanover and Jacob I Sznajder

Circulation research, Vol.98(10), pp.1314-1322

05/26/2006

DOI: 10.1161/01.RES.0000222418.99976.1d

PMID: 16614303

Files and links (1)

url

https://doi.org/10.1161/01.RES.0000222418.99976.1dView

Published (Version of record) Open Access

Abstract

We set out to determine whether cellular hypoxia, via mitochondrial reactive oxygen species, promotes Na,K-ATPase degradation via the ubiquitin-conjugating system. Cells exposed to 1.5% O2 had a decrease in Na,K-ATPase activity and oxygen consumption. The total cell pool of alpha1 Na,K-ATPase protein decreased on exposure to 1.5% O2 for 30 hours, whereas the plasma membrane Na,K-ATPase was 50% degraded after 2 hours of hypoxia, which was prevented by lysosome and proteasome inhibitors. When Chinese hamster ovary cells that exhibit a temperature-sensitive defect in E1 ubiquitin conjugation enzyme were incubated at 40 degrees C and 1.5% O2, the degradation of the alpha1 Na,K-ATPase was prevented. Exogenous reactive oxygen species increased the plasma membrane Na,K-ATPase degradation, whereas, in mitochondrial DNA deficient rho(0) cells and in cells transfected with small interfering RNA against Rieske iron sulfur protein, the hypoxia-mediated Na,K-ATPase degradation was prevented. The catalase/superoxide dismutase (SOD) mimetic (EUK-134) and glutathione peroxidase overexpression prevented the hypoxia-mediated Na,K-ATPase degradation and overexpression of SOD1, but not SOD2, partially inhibited the Na+ pump degradation. Accordingly, we provide evidence that during hypoxia, mitochondrial reactive oxygen species are necessary to degrade the plasma membrane Na,K-ATPase via the ubiquitin-conjugating system.

Cricetinae

Hypoxia - enzymology

Reactive Oxygen Species - metabolism

Cricetulus

Humans

Cells, Cultured

Oxygen Consumption

Rats

Male

Mitochondria - metabolism

Rats, Sprague-Dawley

Hypoxia - metabolism

Cell Membrane - enzymology

Sodium-Potassium-Exchanging ATPase - metabolism

Animals

Lysosomes - metabolism

Ubiquitin-Conjugating Enzymes - metabolism

Proteasome Endopeptidase Complex - metabolism

CHO Cells

Details

Title: Subtitle: Hypoxia-mediated degradation of Na,K-ATPase via mitochondrial reactive oxygen species and the ubiquitin-conjugating system
Creators: Alejandro P Comellas - Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Laura A Dada
Emilia Lecuona
Liuska M Pesce
Navdeep S Chandel
Nancy Quesada
G R Scott Budinger
Ger J Strous
Aaron Ciechanover
Jacob I Sznajder
Resource Type: Journal article
Publication Details: Circulation research, Vol.98(10), pp.1314-1322
DOI: 10.1161/01.RES.0000222418.99976.1d
PMID: 16614303
ISSN: 0009-7330
eISSN: 1524-4571
Grant note: 5F32HL071421 / NHLBI NIH HHS F32 HL071421 / NHLBI NIH HHS P01-HL73641 / NHLBI NIH HHS
Language: English
Date published: 05/26/2006
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Endocrinology and Diabetes; ICTS; Stead Family Department of Pediatrics; Internal Medicine
Record Identifier: 9984093311202771

Metrics

21 Record Views

96 Times Cited - Web of Science