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| Status |
Public on Feb 14, 2018 |
| Title |
HIF and HOIL-1L-mediated PKCζ degradation stabilizes plasma membrane Na,K-ATPase to protect against hypoxia-induced lung injury |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Exposure to hypoxia requires adaptive mechanisms for survival. During acute hypoxia, Na,K-ATPase endocytosis in alveolar epithelial cells (AEC) occurs via protein kinase C zeta (PKCζ) phosphorylation of α1- Na,K-ATPase independently of the hypoxia inducible factor (HIF). However, exaggerated Na,K-ATPase down-regulation leads to cell death. Here we report that during prolonged hypoxia plasma membrane Na,K-ATPase levels were maintained at ~50% of normoxic values due to HIF mediated regulation of HOIL-1L which targets PKCζ for degradation. Silencing HOIL-1L in the lung epithelium prevented PKCζ degradation causing Na,K-ATPase downregulation. Accordingly, HIF regulation of HOIL-1L targets the phosphorylated PKCζ for degradation and serves as an hypoxia-adaptive mechanism to stabilize the Na,K-ATPase avoiding significant lung injury.
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| Overall design |
ATII mRNA profiles of 8-10 weeks old wild-type (WT) and CreSPC/HOIL-1Lfl/fl mice were generated and sequenced by NextSeq 500 High Output reagent kit (Illumina Inc).
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| Contributor(s) |
Sznajder JI, Ciechanover AJ, Dada L, Magnani N, Anekalla KR, Misharin AV |
| Citation(s) |
29109255 |
| |
| Submission date |
Aug 01, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Jacob Iasha Sznajder |
| E-mail(s) |
j-sznajder@northwestern.edu
|
| Organization name |
Northwestern University
|
| Department |
Medicine
|
| Street address |
240 East Huron
|
| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60611 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA396683 |
| SRA |
SRP114498 |
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