Calcium-dependent mitochondrial permeability transition is augmented in the kidney of Goto-Kakizaki diabetic rat.
BACKGROUND
Renal disease associated with diabetes mellitus is a major problem among diabetic patients. The role of mitochondria in the pathogenesis of diabetes has received a large amount of attention in the last years, but many aspects of this subject are still poorly understood. In the present study, we studied the susceptibility of the mitochondrial permeability transition (MPT) on kidney mitochondria from the Goto-Kakizaki (GK) rat, an animal model featuring physiological and pathological alterations characteristic of type 2 diabetes.


METHODS
Kidney mitochondria were isolated by differential centrifugations; mitochondrial electric transmembrane potential and calcium loading capacity were evaluated with a TPP+-selective electrode and with a calcium-sensitive fluorescent probe. Coenzyme Q9, Q10 and vitamin E were evaluated by high-performance liquid chromatography (HPLC).


RESULTS
Kidney mitochondria from the diabetic animals had an increased susceptibility to the induction of the MPT by calcium. We observed a loss of calcium-loading capacity and a higher calcium-induced mitochondrial depolarization. Vitamin E and coenzyme Q9 were also increased in kidney mitochondria from GK rats.


CONCLUSIONS
The results show an enhanced MPT activation in kidney mitochondria from GK rats, which lead us to suggest that this condition may be one major alteration triggered by chronic diabetes in kidney cells, ultimately leading to cell dysfunction.
Oliveira
Paulo J
PJ
Centro de Neurociências de Coimbra, Departamento de Zoologia, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, Portugal. pauloliv@ci.uc.pt
Esteves
Telma C
TC
Seiça
Raquel
R
Moreno
António J M
AJ
Santos
Maria S
MS
D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000150:complications / Q000378:metabolism*; D004195:Disease Models, Animal; D007425:Intracellular Membranes / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012016:Reference Values; D014451:Ubiquinone / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
D014451:Ubiquinone; D014810:Vitamin E; C030571:ubiquinone 9; D002118:Calcium