Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1572-1583 |
| Number of pages | 12 |
| Journal | Laboratory Investigation |
| Volume | 91 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2011 |
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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 journal › Article
TY - JOUR
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
PY - 2011
Y1 - 2011
N2 - 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.
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.
KW - albumin
KW - creatinine
KW - glutathione transferase
KW - glutathione transferase kappa 1
KW - lipid
KW - unclassified drug
U2 - 10.1038/LABINVEST.2011.107
DO - 10.1038/LABINVEST.2011.107
M3 - Article
VL - 91
SP - 1572
EP - 1583
JO - Laboratory Investigation
JF - Laboratory Investigation
SN - 0023-6837
IS - 11
ER -