TY - JOUR
T1 - Functional interactions between oxidative stress, membrane Na+ permeability, and cell volume in rat hepatoma cells
AU - Schlenker, Thorsten
AU - Feranchak, Andrew P.
AU - Schwake, Lukas
AU - Stremmel, Wolfgang
AU - Roman, Richard M.
AU - Fitz, J. Gregory
N1 - Funding Information:
Supported in part by DFG grants SCHL 380/1-1 and SCHL 380/2-1 (to T.S.); Cystic Fibrosis Foundation (to A.P.F.); and National Institutes of Health grants DK43278 and DK46082 and Waterman Foundation (to J.G.F.).
PY - 2000
Y1 - 2000
N2 - Background and Aims: Oxidative stress leads to a rapid initial loss of liver cell volume, but the adaptive mechanisms that serve to restore volume have not been defined. This study aimed to evaluate the functional interactions between oxidative stress, cell volume recovery, and membrane ion permeability. Methods: In HTC rat hepatoma cells, oxidative stress was produced by exposure to H2O2 or D-alanine plus D-amino acid oxidase (40 U/mL). Results: Oxidative stress resulted in a rapid decrease in relative cell volume to 0.85 ± 0.06. This was followed by an ~100-fold increase in membrane cation permeability and partial volume recovery to 0.97 ± 0.05 of original values. The volume-sensitive conductance was permeable to Na+ ≃K+ >> Tris+, and whole-cell current density at -80 mv increased from -1.2 pA/pF at 10-5 mol/L H2O2 to -95.1 pA/pF at 10-2 mol/L H2O2. The effects of H2O2 were completely inhibited by dialysis of the cell interior with reduced glutathione, and were markedly enhanced by inhibition of glutathione synthase. Conclusions: These findings support the presence of dynamic functional interactions between cell volume, oxidative stress, and membrane Na+ permeability. Stress-induced Na+ influx may represent a beneficial adaptive response that partially restores cell volume over short periods, but sustained cation influx could contribute to the increase in intracellular [Na+] and [Ca2+] associated with cell injury and necrosis.
AB - Background and Aims: Oxidative stress leads to a rapid initial loss of liver cell volume, but the adaptive mechanisms that serve to restore volume have not been defined. This study aimed to evaluate the functional interactions between oxidative stress, cell volume recovery, and membrane ion permeability. Methods: In HTC rat hepatoma cells, oxidative stress was produced by exposure to H2O2 or D-alanine plus D-amino acid oxidase (40 U/mL). Results: Oxidative stress resulted in a rapid decrease in relative cell volume to 0.85 ± 0.06. This was followed by an ~100-fold increase in membrane cation permeability and partial volume recovery to 0.97 ± 0.05 of original values. The volume-sensitive conductance was permeable to Na+ ≃K+ >> Tris+, and whole-cell current density at -80 mv increased from -1.2 pA/pF at 10-5 mol/L H2O2 to -95.1 pA/pF at 10-2 mol/L H2O2. The effects of H2O2 were completely inhibited by dialysis of the cell interior with reduced glutathione, and were markedly enhanced by inhibition of glutathione synthase. Conclusions: These findings support the presence of dynamic functional interactions between cell volume, oxidative stress, and membrane Na+ permeability. Stress-induced Na+ influx may represent a beneficial adaptive response that partially restores cell volume over short periods, but sustained cation influx could contribute to the increase in intracellular [Na+] and [Ca2+] associated with cell injury and necrosis.
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U2 - 10.1016/S0016-5085(00)70222-8
DO - 10.1016/S0016-5085(00)70222-8
M3 - Article
C2 - 10648468
AN - SCOPUS:0033973570
SN - 0016-5085
VL - 118
SP - 395
EP - 403
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -