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Hypoxia impairs maturation of the Na,K‐ATPase (LB180)
Author(s) -
Capri Joseph,
Tokhtaeva Elmira,
Sun Haying,
Angulo Martin,
Dada Laura,
Sznajder Jacob,
Kaplan Jack,
Whitelegge Julian,
Vagin Olga
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb180
Subject(s) - western blot , hypoxia (environmental) , atpase , calnexin , chemistry , medicine , biochemistry , microbiology and biotechnology , enzyme , endocrinology , biology , endoplasmic reticulum , gene , oxygen , organic chemistry , calreticulin
Renal tissue hypoxia is a major cause of acute renal failure. The goal of this study was to elucidate the mechanism(s) underlying role of the Na,K‐ATPase in the adaptive response of renal cells to a hypoxic stress. Kidney microsome membranes were isolated from mice exposed to 7% O2 (hypoxia) or to room air for three days, proteins were extracted by a non‐ionic detergent, immunoprecipitated using anti‐Na,K‐ATPase antibodies, and analyzed by nLC‐MS/MS and Western blot analyses. Hypoxia did not change the total amount of the Na,K‐ATPase, as was assessed by comparing the Mascot scores and confirmed by a Western blot analysis. In contrast, hypoxia significantly decreased the amount of the Na,K‐ATPase‐co‐immunoprecipitated ER chaperones and enzymes presumably involved in the maturation of the Na,K‐ATPase, including BiP, Hsp40, calnexin, PDI, glucosidase, mannosidase and DnaJ. Consistent with these results, a significant retention of the Na,K‐ATPase was observed in cultured epithelial cells exposed to hypoxia. The results suggest that the hypoxia‐induced ER retention of the Na,K‐ATPase slows down the maturation and hence the delivery of the newly synthesized pumps to the plasma membrane, resulting in a decrease in ATP consumption as an adaptive response to hypoxia. Grant Funding Source : Supported by 1R01HL113350‐01A1