Attenuation of endoplasmic reticulum stress and mitochondrial injury in kidney with ischemic postconditioning application and trimetazidine treatment.

Abstract : UNLABELLED: ABSTRACT: BACKGROUND: Endoplasmic reticulum (ER) and mitochondria have been implicated in the pathology of renal ischemia/reperfusion (I/R). In the present study, we investigated whether the use of ischemic postconditioning (IPostC) and trimetazidine (TMZ) separately or combined could reduce ER stress and mitochondria damage after renal ischemia. METHODS: Kidneys of Wistar rats were subjected to 60-min of warm ischemia followed by 120-min of reperfusion (I/R group, n = 6), or to 6 cycles of ischemia/reperfusion (10-s each cycle) just after 60-min of warm ischemia (IPostC group, n = 6), or to i.p. injection of TMZ (3 mg/kg) 30-min before ischemia (TMZ group, n = 6), or to the combination of both treatments (IPostC+TMZ group, n = 6). The results of these experimental groups were compared to those of a sham-operated group in which rat renal pedicles were only dissected. Sodium reabsorption rate, creatinine clearance lactate deshydrogenase (LDH) activity in plasma, and concentration of malonedialdehyde (MDA) in tissue were determined. In addition, Western blot analysis was performed to identify the amounts of cytochrome c, c-JunNH2-terminal kinase (JNK), voltage-dependent anion channel (VDAC), glycogen synthase kinase 3-beta (GSK3-β), and ER stress parameters. RESULTS: IPostC or/and TMZ significantly decreased cytolysis, oxidative stress and improved renal function in comparison to I/R group. IPostC but not TMZ significantly attenuated ER stress parameters versus I/R group. Indeed, it down-regulated the glucose-regulated protein 78 (GRP78), the activating transcription factor 4 (ATF4), the RNA activated protein kinase (PKR)-like ER kinas (PERK), the X box binding protein-1 (XBP-1) and the caspase12 protein levels. TMZ treatment significantly augmented GSK3-β phosphorylation and reduced levels of cytochrome c and VDAC phosphorylation in comparison to IPostC application. The combination of both treatments gave a synergetic effect. It significantly improved the survival rate, attenuated cytolysis, oxidative stress and improved renal function. CONCLUSION: This study revealed that IPostC protects kidney from I/R injury by suppressing ER stress while the beneficial effects of TMZ are mediated by mitochondria protection. The combination of both treatments ameliorated functional recovery.
Type de document :
Article dans une revue
Journal of Biomedical Science, BioMed Central, 2012, 19 (1), pp.71. 〈10.1186/1423-0127-19-71〉
Liste complète des métadonnées

Littérature citée [44 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00726655
Contributeur : Ed. Bmc <>
Soumis le : vendredi 31 août 2012 - 01:05:40
Dernière modification le : lundi 30 avril 2018 - 15:20:06
Document(s) archivé(s) le : samedi 1 décembre 2012 - 03:30:24

Fichiers

Identifiants

Collections

Citation

Asma Mahfoudh-Boussaid, Mohamed Zaouali, Thierry Hauet, Kaouther Hadj-Ayed, Abdel-Hédi Miled, et al.. Attenuation of endoplasmic reticulum stress and mitochondrial injury in kidney with ischemic postconditioning application and trimetazidine treatment.. Journal of Biomedical Science, BioMed Central, 2012, 19 (1), pp.71. 〈10.1186/1423-0127-19-71〉. 〈inserm-00726655〉

Partager

Métriques

Consultations de la notice

414

Téléchargements de fichiers

405