Recovery of cellular functions following oxidant injury.
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.
Nowak
G
G
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA.
Aleo
M D
MD
Morgan
J A
JA
Schnellmann
R G
RG
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects*; D007773:Lactates / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D016877:Oxidants / Q000633:toxicity*; D010101:Oxygen Consumption / Q000187:drug effects; D010545:Peroxides / Q000494:pharmacology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D020122:tert-Butylhydroperoxide
D007773:Lactates; D016877:Oxidants; D010545:Peroxides; D005973:Glutamine; D010042:Ouabain; D004247:DNA; D020122:tert-Butylhydroperoxide; D012964:Sodium; D005947:Glucose