info:eu-repo/semantics/article
Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy
Fecha
2012-04-04Registro en:
García, Isabel Mercedes; Altamirano, Berta Liliana; Mazzei, Luciana Jorgelina; Fornes, Miguel Walter; Molina, Marisa Nile; et al.; Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy; American Physiological Society; American Journal Of Physiology-renal Physiology; 302; 12; 4-4-2012; 1565-1605
1931-857X
CONICET Digital
CONICET
Autor
García, Isabel Mercedes
Altamirano, Berta Liliana
Mazzei, Luciana Jorgelina
Fornes, Miguel Walter
Molina, Marisa Nile
Ferder, León
Manucha, Walter Ariel Fernando
Resumen
Vitamin D slows the progression of chronic kidney disease. Furthermore, activators of vitamin D receptors (VDR) have suppressant effects on the renin-angiotensin system, as well as anti-inflammatory and antifibrotic actions. This study aimed to evaluate the cytoprotective effects of paricalcitol, a VDR activator, at the mitochondrial level using an obstructive nephropathy model [unilateral ureteral obstruction (UUO)]. Rats subjected to UUO and controls were treated daily with vehicle or paricalcitol. The control group underwent a sham surgery. The treatment was done for 15 days (30 ng/kg). The following were determined: biochemical parameters; fibrosis; apoptosis; mitochondrial morphology; VDR, AT(1) receptor, and NADPH oxidase 4 expression; and NADPH oxidase activity (in total and in mitochondrial fractions from the renal cortex). VDR activation prevented fibrosis (20 ± 5 vs. 60 ± 10%) and the number of TUNEL-positive apoptotic cells (10 ± 3 vs. 25 ± 4) in UUO. Biochemical, histological, and molecular studies suggest mitochondrial injury. Electron microscopy revealed in UUO electronically luminous material in the nucleus. Some mitochondria were increased in size and contained dilated crests and larger than normal spaces in their interiors. These changes were not present with paricalcitol treatment. Additionally, high AT(1)-receptor mRNA and NADPH activity was reverted in mitochondrial fractions from obstructed paricalcitol-treated animals (0.58 ± 0.06 vs. 0.95 ± 0.05 relative densitometry units and 9,000 ± 800 vs. 15,000 ± 1,000 relative fluorescence units·μg protein(-1)·min(-1), respectively). These changes were consistent with an improvement in VDR expression (0.75 ± 0.05 vs. 0.35 ± 0.04 relative densitometry units). These results suggest that paricalcitol confers a protective effect and reveal, as well, a possible AT(1) receptor-dependent protective effect that occurs at the mitochondrial level.