ID 111127
Author
Nakashita, Yukie Takeda Pharmaceutical Company|Tokushima University
Sano, Tomoya Takeda Pharmaceutical Company
Yoshioka, Hiroaki Takeda Pharmaceutical Company
Shimada, Tomoki Takeda Pharmaceutical Company
Hori, Ryotaro Takeda Pharmaceutical Company
Usami, Makoto Kobe University
Keywords
db/m-5/6 nephrectomized mice
db/db mice
glomerular hyperfiltration
mitochondrial respiratory complex
Content Type
Journal Article
Description
Hyperglycemia induces nonconcordant regulation of renal mitochondrial respiratory complexes, increases oxidative stress, and causes diabetic nephropathy. Hypertension is a complication associated with diabetes and involves glomerular hyperfiltration, the effects of which on mitochondrial respiratory complexes are not well understood. To investigate the effect of glomerular hyperfiltration on renal mitochondrial respiratory complexes, we used the 5/6 nephrectomized BKS.Cg-Dock7m+/+Leprdb/J, Dock7m+/+Leprdb mice (db/m-5/6Nx mice) as a model for glomerular hyperfiltration. The BKS.Cg-Dock7m+/+Leprdb/J, +Leprdb/+Leprdb mice (db/db mice), a model for type 2 diabetes, was used as the positive control. We investigated the activities and protein levels of the mitochondrial complex, and themitochondrial DNA and adenosine triphosphate content in the kidneys of these models. Blood chemistry and renal histopathological examination were performed for characterization of the disease. Both models showed expansion of the mesangial matrix of the glomeruli, which is indicative of glomerular hyperfiltration. The activities of complexes I and IV and the protein levels of complexes I and III were nonconcordant in db/m-5/6Nx mice. In conclusion, we demonstrated that nonconcordant regulation of mitochondrial complexes in db/m-5/6Nx mice involved with glomerular hyperfiltration. The progression and/or severity of nephropathymight be affected through a synergistic effect of mitochondrial dysfunction in hyperglycemia and glomerular hyperfiltration.
Journal Title
The Journal of Medical Investigation
ISSN
13496867
13431420
NCID
AA11166929
AA12022913
Publisher
Faculty of Medicine Tokushima University
Volume
64
Issue
3-4
Start Page
255
End Page
261
Sort Key
255
Published Date
2017-08
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Medical Sciences