Differential Redox Regulation of XXXX Signaling and Viability in Normal and Malignant Prostate Cells.

@entity1 @entity5568 @entity263 @entity5 @entity2569 @entity26 @entity40031 @entity7011 @entity11620 @entity141
UNASSIGNED: In @entity263 , reactive @entity26 species (ROS) are elevated and @entity141 signaling is impaired. Thus, several novel therapeutic strategies have been developed to target  altered ROS and @entity141 signaling pathways in @entity263 . Here, we investigate alterations of intracellular @entity141 and inhibition of cell viability caused by ROS in primary @entity1 prostate epithelial cells (hPECs) from healthy tissue and @entity263 cell lines (LNCaP, DU145, and @entity11620 ). In hPECs, LNCaP and DU145 @entity5568 induces an initial @entity141 increase, which in @entity263 cells is blocked at high concentrations of @entity5568 . Upon depletion of intracellular @entity141 stores, store-operated @entity141 entry (SOCE) is activated. SOCE channels can be formed by hexameric @entity7011 channels; however, @entity7011 can form heteromultimers with its homolog, @entity40031 . Since the redox sensor of @entity7011 ( @entity2569 -195) is absent in @entity40031 , the @entity7011 / @entity40031 ratio in T  cells determines the redox sensitivity of SOCE and cell viability. In @entity263 cells, SOCE is blocked at lower concentrations of @entity5568 compared with hPECs. An analysis of data from hPECs, LNCaP, DU145, and @entity11620 , as well as previously published data from naive and effector TH cells, demonstrates a strong correlation between the @entity7011 / @entity40031 ratio and the SOCE redox sensitivity and cell viability. Therefore, our data support the concept that store-operated @entity141 channels in hPECs and @entity263 cells are heteromeric @entity7011 / @entity40031 channels with an increased @entity7011 / @entity40031 ratio in cells derived from @entity263 @entity5 . In addition, ROS-induced alterations in @entity141 signaling in @entity263 cells may contribute to the higher sensitivity of these cells to ROS.
