Project description:Whole hearts from wild-type and Na,K-ATPase alpha 1 het. mice. Adult male, 8-16 weeks old on a 129/BSwiss background. Keywords: repeat sample
Project description: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.