Mitochondrial Dysfunction in Kidney Cortex and Medulla of Subtotally Nephrectomized Rat
| Autor: | JEDLIČKA, Jan, GRUNDMANOVÁ, Martina, ŠVÍGLEROVÁ, Jitka, TŮMA, Zdeněk, NALOS, Lukáš, RAJDL, Daniel, ŠTENGL, Milan, KUNCOVÁ, Jitka |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Physiol Res |
| ISSN: | 1802-9973 0862-8408 |
| DOI: | 10.33549/physiolres.935000 |
| Popis: | Five-sixths nephrectomy is a widely used experimental model of chronic kidney disease (CKD) that is associated with severe mitochondrial dysfunction of the remnant tissue. In this study, we assessed the effect of CKD on mitochondrial respiration separately in the rat kidney cortex and medulla 10 weeks after induction of CKD by subtotal 5/6 nephrectomy (SNX). Mitochondrial oxygen consumption was evaluated on mechanically permeabilized samples of kidney cortex and medulla using high-resolution respirometry and expressed per mg of tissue wet weight or IU citrate synthase (CS) activity. Mitochondrial respiration in the renal cortex of SNX rats was significantly reduced in all measured respiratory states if expressed per unit wet weight and remained lower if recalculated per IU citrate synthase activity, i.e. per mitochondrial mass. In contrast, the profound decrease in the activity of CS in SNX medulla resulted in significantly elevated respiratory states expressing the OXPHOS capacity when Complexes I and II or II only are provided with electrons, LEAK respiration after oligomycin injection, and Complex IV-linked oxygen consumption per unit CS activity suggesting compensatory hypermetabolic state in remaining functional mitochondria that is not sufficient to fully compensate for respiratory deficit expressed per tissue mass. The results document that CKD induced by 5/6 nephrectomy in the rat is likely to cause not only mitochondrial respiratory dysfunction (in the kidney cortex), but also adaptive changes in the medulla that tend to at least partially compensate for mitochondria loss. |
| Databáze: | OpenAIRE |
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