Differential effects of EGF on repair of cellular functions after dichlorovinyl-L-cysteine-induced injury

This study examined the repair of renal proximal tubule cellular (RPTC) fun ctions following sublethal injury induced by the nephrotoxicant S-(1,2-dich lorovinyl)-L-cysteine (DCVC). DCVC exposure resulted in 31% cell death and loss 24 h following the treatment. Manolayer confluence recovered through m igration/spreading but not proliferation after 6 days. Basal, uncoupled, an d ouabain-sensitive oxygen consumption (Qo(2)) decreased 47, 76, and 62%, r espectively, 24 h after DCVC exposure. Na+-K+-ATPase activity and Na+-depen dent glucose uptake were inhibited 80 and 68%, respectively, 24 h after DCV C exposure. None of these functions recovered over time. Addition of epider mal growth factor (EGF) following DCVC exposure did not prevent decreases i n basal, uncoupled, and ouabain-sensitive Qo(2) values and Na+-K+-ATPase ac tivity but promoted their recovery over 4-6 days. In contrast, no recovery of Na+-dependent glucose uptake occurred in the presence of EGF. These data show that: 1) DCVC exposure decreases mitochondrial function, Na+-K+-ATPas e activity, active Na+ transport, and Na+-dependent glucose uptake in suble thally injured RPTC; 2) DCVC-treated RPTC do not proliferate nor regain the ir physiological functions in this model; and 3) EGF promotes recovery of m itochondrial function and active Na+ transport but not Na+-dependent glucos e uptake. These results suggest that cysteine conjugates may cause renal dy sfunction, in part, by decreasing RPTC functions and inhibiting their repai r.