Glutathione transferase kappa deficiency causes glomerular nephropathy without overt oxidative stress
Date
2011
Authors
Blackburn, Anneke
Coggan, Marjorie
Shield, Alison
Cappello, Jean
Theodoratos, Angelo
Murray, Tracy
Rooke, Melissa
Larter, Claire
Koina, Mark
Matthaei, Klaus
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Lippincott Williams & Wilkins
Abstract
Glutathione transferase kappa (GSTK1-1) is a highly conserved, mitochondrial enzyme potentially involved in redox reactions. GSTK1-1-deficient mice were generated to further study the enzyme's biological role. Reduced and total glutathione levels in liver and kidney were unchanged by GSTK1-1 deficiency and NADPH quinone oxidoreductase 1 expression was not elevated indicating that there is no general underlying oxidative stress in Gstk1 / mice. Electron microscopy of liver and kidney showed no changes in mitochondrial morphology with GSTK1-1 deficiency. The death of a number of Gstk1 / males with urinary tract problems prompted close examination of the kidneys. Electron microscopy revealed glomerular basement membrane changes at 3 months, accompanied by detectable microalbuminuria in male mice (albumin:creatinine ratio of 2.660.83 vs 1.130.20 mg/mmol for Gstk1 / and wild-type (WT), respectively, P0.001). This was followed by significant foot process effacement (40-55% vs 10% for Gstk1 / and WT, respectively) at 6 months of age in all Gstk1 / mice examined. Kidney tubules were ultrastructurally normal. Compared with human disease, the Gstk1 / kidneys show changes seen in glomerulopathies causing nephrotic syndrome. Gstk1 / mice may offer insights into the early development of glomerular nephropathies.
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Keywords
Keywords: albumin; creatinine; glutathione transferase; glutathione transferase kappa 1; lipid; unclassified drug; animal experiment; animal model; animal tissue; article; blood analysis; body weight; cell structure; electron microscopy; enzyme deficiency; glomerul glomerular nephropathy; glutathione transferase kappa; GSTK1-1 deficiency; knockout mice; mitochondria
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Laboratory Investigation
Type
Journal article
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2037-12-31