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Attenuation of endoplasmic reticulum stress and mitochondrial injury in kidney with ischemic postconditioning application and trimetazidine treatment
- Source :
- Journal of Biomedical Science, Journal of Biomedical Science, BioMed Central, 2012, 19 (1), pp.71. ⟨10.1186/1423-0127-19-71⟩, Digital.CSIC. Repositorio Institucional del CSIC, instname, Journal of Biomedical Science, Vol 19, Iss 1, p 71 (2012)
- Publication Year :
- 2012
-
Abstract
- This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.<br />[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.<br />This work was supported by the Tunisian Ministry of Higher Education and Scientific Research and The Spanish Ministry of Foreign Affairs and Cooperation/ AECID (A/031197/10).
- Subjects :
- [SDV]Life Sciences [q-bio]
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Ischemia
Trimetazidine
lcsh:Medicine
ComputingMilieux_LEGALASPECTSOFCOMPUTING
Pharmacology
medicine.disease_cause
Kidney
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Pharmacology (medical)
Rats, Wistar
Molecular Biology
Endoplasmic Reticulum Chaperone BiP
030304 developmental biology
Biochemistry, medical
[SDV.IB] Life Sciences [q-bio]/Bioengineering
0303 health sciences
Ischemic postconditioning
Renal ischemia
Chemistry
4. Education
Research
Ischemia-reperfusion
lcsh:R
Biochemistry (medical)
Cell Biology
General Medicine
medicine.disease
Endoplasmic Reticulum Stress
Protein kinase R
3. Good health
Mitochondria
Rats
[SDV] Life Sciences [q-bio]
medicine.anatomical_structure
030220 oncology & carcinogenesis
Reperfusion Injury
Unfolded protein response
[SDV.IB]Life Sciences [q-bio]/Bioengineering
Reperfusion injury
Oxidative stress
medicine.drug
Subjects
Details
- ISSN :
- 14230127 and 10217770
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Journal of biomedical science
- Accession number :
- edsair.doi.dedup.....d469a47978dab19873686f4679f8bc93