This study examined the repair of renal proximal tubule cellular (RPTC) functions following sublethal injury induced by the nephrotoxicant S-(1,2-dichlorovinyl)-L-cysteine (DCVC). DCVC exposure resulted in 31% cell death and loss 24 h following the treatment. Monolayer confluence recovered through migration/spreading but not proliferation after 6 days. Basal, uncoupled, and ouabain-sensitive oxygen consumption (QO₂) decreased 47, 76, and 62%, respectively, 24 h after DCVC exposure. Na⁺-K⁺-ATPase activity and Na⁺-dependent glucose uptake were inhibited 80 and 68%, respectively, 24 h after DCVC exposure. None of these functions recovered over time. Addition of epidermal growth factor (EGF) following DCVC exposure did not prevent decreases in basal, uncoupled, and ouabain-sensitive QO₂ values and Na⁺-K⁺-ATPase activity 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⁺-ATPase activity, active Na⁺ transport, and Na⁺-dependent glucose uptake in sublethally injured RPTC; 2) DCVC-treated RPTC do not proliferate nor regain their physiological functions in this model; and 3) EGF promotes recovery of mitochondrial function and active Na⁺ transport but not Na⁺-dependent glucose uptake. These results suggest that cysteine conjugates may cause renal dysfunction, in part, by decreasing RPTC functions and inhibiting their repair.

renal proximal tubular cells; cysteine conjugate; S-(1,2-dichlorovinyl)-L-cysteine; sublethal cell injury; regeneration; cell repair; mitochondrial function; oxygen consumption; sodium-potassium adenosinetriphosphatase; active sodium transport; sodium-coupled glucose uptake; ascorbic acid; epidermal growth factor

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