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-1α (HIF-1α) 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 NG-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-1α 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: 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-1α stabilization. The beneficial impact of IPC was abolished when NO production is inhibited before IPC application.
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Authors | Asma Mahfoudh-Boussaid, Mohamed Amine Zaouali, Kaouther Hadj-Ayed, Abdel-Hédi Miled, Dalila Saidane-Mosbahi, Joan Rosello-Catafau, Hassen Ben Abdennebi |
Journal | Journal of biomedical science
(J Biomed Sci)
Vol. 19
Pg. 7
(Jan 17 2012)
ISSN: 1423-0127 [Electronic] England |
PMID | 22252226
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Atf4 protein, rat
- Endoplasmic Reticulum Chaperone BiP
- GRP78 protein, rat
- HSPA5 protein, human
- Heat-Shock Proteins
- Hif1a protein, rat
- Hypoxia-Inducible Factor 1, alpha Subunit
- TNF Receptor-Associated Factor 2
- Activating Transcription Factor 4
- Nitric Oxide
- Nitric Oxide Synthase Type III
- Nos3 protein, rat
- Akt1 protein, rat
- PERK kinase
- Proto-Oncogene Proteins c-akt
- eIF-2 Kinase
- NG-Nitroarginine Methyl Ester
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Topics |
- Activating Transcription Factor 4
(metabolism)
- Animals
- Blotting, Western
(veterinary)
- Endoplasmic Reticulum Chaperone BiP
- Endoplasmic Reticulum Stress
- Heat-Shock Proteins
(metabolism)
- Hypoxia-Inducible Factor 1, alpha Subunit
(genetics, metabolism)
- Injections, Intravenous
(veterinary)
- Ischemic Preconditioning
(veterinary)
- Kidney
(physiopathology)
- Male
- NG-Nitroarginine Methyl Ester
(pharmacology)
- Nitric Oxide
(metabolism)
- Nitric Oxide Synthase Type III
(metabolism)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Rats
- Rats, Wistar
- Reperfusion Injury
(physiopathology, veterinary)
- TNF Receptor-Associated Factor 2
(metabolism)
- Up-Regulation
- eIF-2 Kinase
(metabolism)
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