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 (PKC) phosphorylation of 1- 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 PKC for degradation. Silencing HOIL-1L in the lung epithelium prevented PKC degradation causing Na,K-ATPase downregulation.  Accordingly, HIF regulation of HOIL-1L targets the phosphorylated PKC for degradation and serves as an hypoxia-adaptive mechanism to stabilize the Na,K-ATPase avoiding significant lung injury. SOURCE: Jacob,Iasha,Sznajder (j-sznajder@northwestern.edu) -  Northwestern University

Pluto Bioinformatics

GSE102107: HIF and HOIL-1L-mediated PKC degradation stabilizes plasma membrane Na,K-ATPase to protect against hypoxia-induced lung injury