Hypoxia-induced endocytosis of Na,K-ATPase in alveolar epithelial cells is mediated by mitochondrial reactive oxygen species and PKC-ζ

Impairment of Na+,K+-ATPase in CD95(APO-1)-induced human T-cell leukemia cell apoptosis mediated by glutathione depletion and generation of hydrogen peroxide

“…27 This short-term regulation facilitates cells to promptly respond to the acute changes in intracellular ion environment. 23,27 We describe here for the first time that Fas L can cause an irreversible internalization of Na þ ,K þ -ATPase as a mechanism to suppress its activity, suggesting that this process is probably not relevant to the routine short-term regulation of sodium pump, but rather allows cells to rapidly undergo apoptosis. We speculate that this internalization of Na þ ,K þ -ATPase is necessary for malignant T-cell deletion, since it can greatly increase the sensitization of abnormal T cells to Fas/Fas L system-induced cell apoptosis.…”

“…In summary, these data suggest that intracellular GSH depletion produces H 2 O 2 , then Effects of Fas L, GSH, BSO and H 2 O 2 on the serine phosphorylation of Na þ ,K þ -ATPase a1 subunit Considerable evidence has documented that the 'endocytosis' of Na þ ,K þ -ATPase is closely related to serine phosphorylation of Na þ ,K þ -ATPase a1 subunit, the process of which is tightly Impairment of Na þ ,K þ -ATPase in human T-cell leukemia cell apoptosis W Yin et al controlled by intracellular protein kinase C (PKC) isoforms. 22,23 In present study, we performed immunoprecipitation experiment to observe the effects of Fas L, GSH, BSO and H 2 O 2 on serine phosphorylation of Na þ ,K þ ATPase a1 subunit. The results, as shown in Figure 7a, revealed that both Fas L and BSO increased the serine phosphorylation of Na þ ,K þ ATPase a1 subunit, whereas GSH decreased it.…”

Gene regulation in the adaptive process to hypoxia in lung epithelial cells

“…Both in vitro and in vivo studies clearly show that decreased O 2 tension reduces the capacity of alveolar epithelial cells to actively transport sodium across alveolar epithelium. In alveolar epithelial cells, hypoxia (0% and 3% O 2 ) inhibits dome formation, decreases both amiloridesensitive 22 Na influx and Na-K-ATPase activity (14,32,41,42), and reduces amiloride-sensitive short-circuit current (32), suggesting that transepithelial sodium transport is impaired. The mechanisms whereby hypoxia decreases transepithelial sodium transport depends on the severity and the length of the hypoxic exposure.…”

“…Several studies in alveolar epithelial cells indicate that hypoxia alters the trafficking of sodium proteins between the cytosol and the membrane. In A549 cells, hypoxia (1.5% O 2 for 60 min) decreased Na-KATPase activity by promoting the endocytosis of ␣ 1 and ␤ 1 Na-K-ATPase protein subunits (14). Planès et al (40) reported that during moderate hypoxia (3% O 2 for 18 h), the decrease in sodium channels in the apical membrane was restored by ␤ 2 -agonists, which favored the trafficking of proteins from the cytosol to the membrane.…”

“…Several possibilities that are not exclusive have been evoked. Dada and coworkers (14) reported that during severe and short-term hypoxia, mitochondrial ROS activate PKC-, which phosphorylates Na-K-ATPase pumps at the plasma membrane and decreases Na-K-ATPase activity. More recently, the same group showed that hypoxia-induced plasma membrane Na-K-ATPase degradation required the functional pVHL E3 ligase and Ubc5 (13,70).…”