1. Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxide
- Author
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Hassen Ben Abdennebi, Dalila Saidane-Mosbahi, Mohamed Amine Zaouali, Kaouther Hadj-Ayed, Abdelhedi Miled, Joan Roselló-Catafau, and Asma Mahfoudh-Boussaid
- Subjects
Male ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,lcsh:Medicine ,ischemia-reperfusion ,chemistry.chemical_compound ,eIF-2 Kinase ,Enos ,eNOS, HIF1-α ,Medicine ,Pharmacology (medical) ,Ischemic Preconditioning ,Endoplasmic Reticulum Chaperone BiP ,Heat-Shock Proteins ,Kidney ,biology ,General Medicine ,Endoplasmic Reticulum Stress ,Up-Regulation ,medicine.anatomical_structure ,NG-Nitroarginine Methyl Ester ,Reperfusion Injury ,Injections, Intravenous ,ER stress ,medicine.medical_specialty ,kidney ,Nitric Oxide Synthase Type III ,Blotting, Western ,Nitric Oxide ,Nitric oxide ,Internal medicine ,parasitic diseases ,Animals ,cardiovascular diseases ,Rats, Wistar ,Molecular Biology ,Protein kinase B ,Biochemistry, medical ,Renal sodium reabsorption ,business.industry ,Research ,Akt ,lcsh:R ,Biochemistry (medical) ,Cell Biology ,medicine.disease ,biology.organism_classification ,Hypoxia-Inducible Factor 1, alpha Subunit ,TNF Receptor-Associated Factor 2 ,Activating Transcription Factor 4 ,Rats ,Endocrinology ,chemistry ,Unfolded protein response ,Ischemic preconditioning ,business ,Reperfusion injury ,Proto-Oncogene Proteins c-akt - Abstract
Background: Although recent studies indicate that renal ischemic preconditioning (IPC) protects the kidney from ischemia-reperfusion (I/R) injury, the precise protective mechanism remains unclear. In the current study, we investigated whether early IPC could upregulate hypoxia inducible transcription factor-1 (HIF-1) expression and could reduce endoplasmic reticulum (ER) stress after renal I/R and whether pharmacological inhibition of nitric oxide (NO) production would abolish these protective effects. Methods. Kidneys of Wistar rats were subjected to 60 min of warm ischemia followed by 120 min of reperfusion (I/R group), or to 2 preceding cycles of 5 min ischemia and 5 min reperfusion (IPC group), or to intravenously injection of N G-nitro-L- arginine methylester (L-NAME, 5 mg/kg) 5 min before IPC (L-NAME+IPC group). The results of these experimental groups were compared to those of a sham-operated group. Sodium reabsorption rate, creatinine clearance, plasma lactate dehydrogenase (LDH) activity, tissues concentrations of malonedialdehyde (MDA), HIF-1 and nitrite/nitrate were determined. In addition, Western blot analyses were performed to identify the amounts of Akt, endothelial nitric oxide synthase (eNOS) and ER stress parameters. Results: IPC decreased cytolysis, lipid peroxidation and improved renal function. Parallely, IPC enhanced Akt phosphorylation, eNOS, nitrite/nitrate and HIF-1 levels as compared to I/R group. Moreover, our results showed that IPC increased the relative amounts of glucose-regulated protein 78 (GRP78) and decreased those of RNA activated protein kinase (PKR)-like ER kinase (PERK), activating transcription factor 4 (ATF4) and TNF-receptor-associated factor 2 (TRAF2) as judged to I/R group. However, pre treatment with L-NAME abolished these beneficial effects of IPC against renal I/R insults. Conclusion: These findings suggest that early IPC protects kidney against renal I/R injury via reducing oxidative and ER stresses. These effects are associated with phosphorylation of Akt, eNOS activation and NO production contributing thus to HIF-1 stabilization. The beneficial impact of IPC was abolished when NO production is inhibited before IPC application. © 2012 Mahfoudh-Boussaid et al; licensee BioMed Central Ltd., 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).
- Published
- 2012