Differential Effects of Hsc70 and Hsp70 on Murine ENaC Expression in Epithelial Cells

The epithelial sodium channel (ENaC) has an important role in the regulation of blood pressure and in the function of the pulmonary epithelia. Little is know about the role of the 70 kDa molecular chaperones Hsc70 and Hsp70 in the regulation of ENaC expression. In Xenopus oocytes, we have previously observed that overexpression of Hsc70 inhibits murine ENaC (mENaC) functional and surface expression. In contrast, Hsp70 can either enhance or inhibit mENaC functional and surface expression depending on the extent of overexpression. We hypothesized that these differential effects of Hsc70 and Hsp70 on mENaC expression would also occur in epithelial cells. To test this hypothesis, we constructed MDCK cell lines with stable expression of α-HA, β-V5, γ-Myc-mENaC and tetracycline-inducible expression of either Hsc70 or Hsp70 containing C-terminal myc/His epitope-tags. Tetracycline-induced overexpression of Hsc70 decreased whole cell expression of β(V5)-mENaC. In contrast, lower amounts of tetracycline-induced Hsp...