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

Journal of Biomedical Science

Research

Mohamed Amine Zaouali¹  Joan Rosello-Catafau¹  Thierry Hauet²  Abdel-Hédi Miled³  Sonia Ghoul-Mazgar⁴  Dalila Saidane-Mosbahi⁵  Asma Mahfoudh-Boussaid⁵  Hassen Ben Abdennebi⁵  Kaouther Hadj-Ayed⁵ 

[1] Department of experimental pathology, Hepatic ischemia reperfusion unit, IIBB-CSIC, Barcelona, Spain;Inserm U927, faculty of medicine and pharmacy, university of Poitiers, Poitiers, France;Laboratory of biochemistry, faculty of pharmacy, university of Monastir, Monastir, Tunisia;Laboratory of histology and embryology, faculty of dental medicine, university of Monastir, Monastir, Tunisia;Laboratory of human physiology, faculty of pharmacy, university of Monastir, 5000, Rue Avicenne, Monastir, Tunisia;

关键词: Kidney;    Ischemia-reperfusion;    Ischemic postconditioning;    Trimetazidine;    Endoplasmic reticulum stress;    Mitochondria;   

DOI  :  10.1186/1423-0127-19-71

 received in 2012-01-27, accepted in 2012-07-23,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundEndoplasmic 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.MethodsKidneys 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.ResultsIPostC 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.ConclusionThis 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.

【 授权许可】

Unknown   
© Mahfoudh-Boussaid et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.