Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxide
<p>Abstract</p> <p>Background</p> <p>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 ea...
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| Format: | Article |
| Language: | English |
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BMC
2012-01-01
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| Series: | Journal of Biomedical Science |
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| Online Access: | http://www.jbiomedsci.com/content/19/1/7 |
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| author | Mahfoudh-Boussaid Asma Zaouali Mohamed Hadj-Ayed Kaouther Miled Abdel-Hédi Saidane-Mosbahi Dalila Rosello-Catafau Joan Abdennebi Hassen |
| author_facet | Mahfoudh-Boussaid Asma Zaouali Mohamed Hadj-Ayed Kaouther Miled Abdel-Hédi Saidane-Mosbahi Dalila Rosello-Catafau Joan Abdennebi Hassen |
| author_sort | Mahfoudh-Boussaid Asma |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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<sup>G</sup>-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.</p> <p>Results</p> <p>IPC decreased cytolysis, lipid peroxidation and improved renal function. Parallely, IPC enhanced Akt phosphorylation, eNOS, nitrite/nitrate and HIF-1α 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.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-12-10T12:35:20Z |
| format | Article |
| id | doaj.art-8747e77dc81b4dad891e31462ccbf37a |
| institution | Directory Open Access Journal |
| issn | 1021-7770 1423-0127 |
| language | English |
| last_indexed | 2024-12-10T12:35:20Z |
| publishDate | 2012-01-01 |
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| spelling | doaj.art-8747e77dc81b4dad891e31462ccbf37a2022-12-22T01:48:41ZengBMCJournal of Biomedical Science1021-77701423-01272012-01-01191710.1186/1423-0127-19-7Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxideMahfoudh-Boussaid AsmaZaouali MohamedHadj-Ayed KaoutherMiled Abdel-HédiSaidane-Mosbahi DalilaRosello-Catafau JoanAbdennebi Hassen<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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<sup>G</sup>-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.</p> <p>Results</p> <p>IPC decreased cytolysis, lipid peroxidation and improved renal function. Parallely, IPC enhanced Akt phosphorylation, eNOS, nitrite/nitrate and HIF-1α 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.</p> <p>Conclusion</p> <p>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.</p>http://www.jbiomedsci.com/content/19/1/7kidneyischemia-reperfusionischemic preconditioningAkteNOS, HIF1-αER stress |
| spellingShingle | Mahfoudh-Boussaid Asma Zaouali Mohamed Hadj-Ayed Kaouther Miled Abdel-Hédi Saidane-Mosbahi Dalila Rosello-Catafau Joan Abdennebi Hassen Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxide Journal of Biomedical Science kidney ischemia-reperfusion ischemic preconditioning Akt eNOS, HIF1-α ER stress |
| title | Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxide |
| title_full | Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxide |
| title_fullStr | Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxide |
| title_full_unstemmed | Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxide |
| title_short | Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxide |
| title_sort | ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor 1α in ischemic kidney the role of nitric oxide |
| topic | kidney ischemia-reperfusion ischemic preconditioning Akt eNOS, HIF1-α ER stress |
| url | http://www.jbiomedsci.com/content/19/1/7 |
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