Ascorbic acid promotes recovery of cellular functions following toxicant-induced injury.
We have shown that renal proximal tubular cells (RPTC) recover cellular functions following sublethal injury induced by the oxidant t-butylhydroperoxide but not by the nephrotoxic cysteine conjugate dichlorovinyl-L-cysteine (DCVC). This study investigated whether L-ascorbic acid phosphate (AscP) promotes recovery of RPTC functions following DCVC-induced injury. DCVC exposure (200 microM; 100 min) resulted in 60% RPTC death and loss from the monolayer at 24 h independent of physiological (50 microM) or pharmacological (500 microM) AscP concentrations. Likewise, the DCVC-induced decrease in mitochondrial function (54%), active Na(+) transport (66%), and Na(+)-K(+)-ATPase activity (77%) was independent of the AscP concentration. Analysis of Na(+)-K(+)-ATPase protein expression and distribution in the plasma membrane using immunocytochemistry and confocal laser scanning microscopy revealed the loss of Na(+)-K(+)-ATPase protein from the basolateral membrane of RPTC treated with DCVC. DCVC-injured RPTC cultured in the presence of 50 microM AscP did not proliferate nor recover their physiological functions over time. In contrast, RPTC cultured in the presence of 500 microM AscP proliferated, recovered all examined physiological functions, and the basolateral membrane expression of Na(+)-K(+)-ATPase by day 4 following DCVC injury. These results demonstrate that pharmacological concentrations of AscP do not prevent toxicant-induced cell injury and death but promote complete recovery of mitochondrial function, active Na(+) transport, and proliferation following toxicant-induced injury.
Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, Arkansas 72205-7199, USA.
G
G
Nowak
C A
CA
Carter
R G
RG
Schnellmann
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D003545:Cysteine / Q000031:analogs & derivatives* / Q000633:toxicity; D004247:DNA / Q000032:analysis; D005260:Female; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000975:Antioxidants; C039961:S-(1,2-dichlorovinyl)cysteine; D003094:Collagen; D004247:DNA; D000254:Sodium-Potassium-Exchanging ATPase; D003545:Cysteine; D001205:Ascorbic Acid