1. Nonconcordant regulation of mitochondrial respiratory complexes in the kidneys of 5/6 nephrectomized mice
- Author
-
Makoto Usami, Tomoya Sano, Tomoki Shimada, Hiroaki Yoshioka, Yukie Nakashita, Ryotaro Hori, and Yasuhiro Hamada
- Subjects
Male ,0301 basic medicine ,Mitochondrial DNA ,medicine.medical_specialty ,Kidney ,urologic and male genital diseases ,medicine.disease_cause ,Nephrectomy ,General Biochemistry, Genetics and Molecular Biology ,Nephropathy ,Electron Transport Complex IV ,Diabetic nephropathy ,Mice ,03 medical and health sciences ,Internal medicine ,Diabetes mellitus ,medicine ,Animals ,Diabetic Nephropathies ,Respiratory system ,Electron Transport Complex I ,Chemistry ,General Medicine ,medicine.disease ,Mitochondria ,030104 developmental biology ,Endocrinology ,Blood chemistry ,Hyperglycemia ,Glomerular hyperfiltration ,Oxidative stress - Abstract
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 the mitochondrial 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 nephropathy might be affected through a synergistic effect of mitochondrial dysfunction in hyperglycemia and glomerular hyperfiltration. J. Med. Invest. 64: 255-261, August, 2017.
- Published
- 2017