Glutathione transferase kappa deficiency causes glomerular nephropathy without overt oxidative stress

Anneke Blackburn, Marjorie Coggan, Alison Shield, Jean Cappello, Angelo Theodoratos, Tracy Murray, Melissa Rooke, Claire Larter, Mark Koina, Jane Dahlstrom, Klaus Matthaei, Philip Board

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 2.66±0.83 vs 1.13±0.20 mg/mmol for Gstk1−/− and wild-type (WT), respectively, P=0.001). 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.
Original languageEnglish
Pages (from-to)1572-1583
Number of pages12
JournalLaboratory Investigation
Volume91
Issue number11
DOIs
Publication statusPublished - 2011

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Glutathione Transferase
Oxidative Stress
Kidney
Electron Microscopy
Kidney Tubules
Glomerular Basement Membrane
Liver
Kidney Diseases
Nephrotic Syndrome
Enzymes
Urinary Tract
NADP
Oxidation-Reduction
Glutathione
Foot
Albumins
Creatinine
Oxidoreductases

Cite this

Blackburn, Anneke ; Coggan, Marjorie ; Shield, Alison ; Cappello, Jean ; Theodoratos, Angelo ; Murray, Tracy ; Rooke, Melissa ; Larter, Claire ; Koina, Mark ; Dahlstrom, Jane ; Matthaei, Klaus ; Board, Philip. / Glutathione transferase kappa deficiency causes glomerular nephropathy without overt oxidative stress. In: Laboratory Investigation. 2011 ; Vol. 91, No. 11. pp. 1572-1583.
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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 2.66±0.83 vs 1.13±0.20 mg/mmol for Gstk1−/− and wild-type (WT), respectively, P=0.001). 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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Blackburn, A, Coggan, M, Shield, A, Cappello, J, Theodoratos, A, Murray, T, Rooke, M, Larter, C, Koina, M, Dahlstrom, J, Matthaei, K & Board, P 2011, 'Glutathione transferase kappa deficiency causes glomerular nephropathy without overt oxidative stress', Laboratory Investigation, vol. 91, no. 11, pp. 1572-1583. https://doi.org/10.1038/LABINVEST.2011.107

Glutathione transferase kappa deficiency causes glomerular nephropathy without overt oxidative stress. / Blackburn, Anneke; Coggan, Marjorie; Shield, Alison; Cappello, Jean; Theodoratos, Angelo; Murray, Tracy; Rooke, Melissa; Larter, Claire; Koina, Mark; Dahlstrom, Jane; Matthaei, Klaus; Board, Philip.

In: Laboratory Investigation, Vol. 91, No. 11, 2011, p. 1572-1583.

Research output: Contribution to journalArticle

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T1 - Glutathione transferase kappa deficiency causes glomerular nephropathy without overt oxidative stress

AU - Blackburn, Anneke

AU - Coggan, Marjorie

AU - Shield, Alison

AU - Cappello, Jean

AU - Theodoratos, Angelo

AU - Murray, Tracy

AU - Rooke, Melissa

AU - Larter, Claire

AU - Koina, Mark

AU - Dahlstrom, Jane

AU - Matthaei, Klaus

AU - Board, Philip

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AB - 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 2.66±0.83 vs 1.13±0.20 mg/mmol for Gstk1−/− and wild-type (WT), respectively, P=0.001). 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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