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yna
Nowak1,1 Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205-7199; and 2 Pfizer, Central Research Division, Groton, Connecticut 06340
This study investigated the recovery of renal proximal tubule cellular (RPTC) functions following oxidant-induced sublethal injury. tert-Butylhydroperoxide (TBHP) treatment resulted in 24% cell death and loss 4 h following the exposure. The remaining sublethally injured RPTC proliferated, and monolayer DNA content returned to control values on day 4 following TBHP exposure. Basal oxygen consumption (QO2) and ATP content in sublethally injured RPTC were decreased 64 and 63%, respectively, at 4 h and returned to control values on day 6. Net lactate consumption decreased 71% at 4 h and returned to control values on day 4. In contrast, net glutamine consumption increased 2.7-fold at 4 h and returned to control values on day 6. Ouabain-sensitive QO2, Na+-K+-adenosinetriphosphatase (Na+-K+-ATPase) activity, and Na+-coupled glucose transport were inhibited 77, 88, and 83%, respectively, at 4 h and recovered to control values on day 6. These data show that 1) mitochondrial function, Na+-K+-ATPase activity, active Na+ transport, and Na+-coupled glucose transport are decreased in sublethally injured RPTC following oxidant exposure and are repaired over time; 2) monolayer regeneration precedes the recovery of mitochondrial and transport functions, and 3) sublethal injury and subsequent regeneration are associated with alterations in metabolic substrate utilization. These results suggest that oxidant-induced sublethal injury to RPTC may contribute to renal dysfunction and that RPTC can repair and regain cellular functions following oxidant injury.
renal proximal tubular cells; tert-butylhydroperoxide; cell death; sublethal cell injury; regeneration; cell repair; mitochondrial functions; oxygen consumption; sodium-potassium-adenosinetriphosphatase; active sodium transport; sodium-coupled glucose transport; ascorbic acid; amino acids; glutamine
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