Increased expression of glutathione S-transferase in renal proximal tubules in the early stages of diabetes: a study of type-2 diabetes in the Akita mouse model.
OBJECTIVE
The objective of this study was to examine whether the gene expression profile in the kidney is modified by hyperglycemia in the early stage of diabetes.


METHODS
We analyzed the expression of kidney mRNAs using cDNA array membranes including 588 genes in the kidney of the Akita mouse, a model of type-2 diabetes, after exposure to hyperglycemia for a moderate length of time, but before the manifestation of diabetic glomerulosclerosis. Western blot analysis and immunohistochemical studies were performed to confirm whether the protein for the increasingly expressed mRNA was highly expressed in the kidney of the diabetic mouse.


RESULTS
Two of the 10 detected mRNAs, glutathione S-transferase (GST) alpha and mu, in the kidneys from diabetic mice showed a more than twofold increased expression in comparison to those of control mice. Western blot analysis in kidney tissue extracts confirmed increases in GST alpha and mu at protein levels in the diabetic mice. Immunohistochemical studies revealed strong staining for those proteins in the proximal tubules of diabetic mice.


CONCLUSIONS
These data collectively indicate that expression of GSTs is increased in epithelial cells in proximal tubules even at the early stage of diabetes, probably in response to oxidative stress triggered by hyperglycemia or other toxic effects of glucose.
Fujita
H
H
Department of Hygiene, Akita University School of Medicine, Akita, Japan.
Haseyama
T
T
Kayo
T
T
Nozaki
J
J
Wada
Y
Y
Ito
S
S
Koizumi
A
A
D000818:Animals; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000503:physiopathology; D018450:Disease Progression; D005982:Glutathione Transferase / Q000378:metabolism*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D013194:Staining and Labeling
D007527:Isoenzymes; D012333:RNA, Messenger; D005982:Glutathione Transferase