Oxidative stress in a novel model of chronic acidosis in LLC-PK1 cells.
Chronic metabolic acidosis occurs commonly in chronic renal failure (CRF). The proximal renal tubular cell is the site in the kidney of high oxidative metabolic activity and in CRF is associated with adaptive hypertrophy and hypermetabolism. We hypothesised that chronic acidosis may lead to increased generation of reactive oxygen species due to increased oxidative activity. We developed a novel model of chronic acidosis in LLC-PK1 cells and measured markers of oxidative stress and metabolism. Acidosis led to a reduction in cellular total glutathione and protein thiol content and an increase in glutathione peroxidase activity and NH3 generation. The expression of constitutively expressed heat stress protein (HSP) HSC70 and HSP60 increased at pH 7.0.
Rustom
Rana
R
Department of Medicine, Liverpool University, Liverpool, UK. rana.rustom@liv.ac.uk
Wang
Bohan
B
McArdle
Frank
F
Shalamanova
Liliana
L
Alexander
John
J
McArdle
Anne
A
Thomas
Carol E
CE
Bone
J Michael
JM
Shenkin
Alan
A
Jackson
Malcolm J
MJ
D000138:Acidosis / Q000378:metabolism*; D000143:Acids / Q000494:pharmacology; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018834:Chaperonin 60 / Q000378:metabolism; D002908:Chronic Disease; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018374:LLC-PK1 Cells; D008954:Models, Biological; D018384:Oxidative Stress; D010539:Permeability / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013552:Swine
D000143:Acids; D015415:Biomarkers; D018834:Chaperonin 60; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D011506:Proteins; D013438:Sulfhydryl Compounds; D000641:Ammonia; D005979:Glutathione Peroxidase; D005978:Glutathione