Melatonin Modulates Endoplasmic Reticulum Stress and Akt/GSK3-Beta Signaling Pathway in a Rat Model of Renal Warm Ischemia Reperfusion
Melatonin (Mel) is widely used to attenuate ischemia/reperfusion (I/R) injury in several organs. Nevertheless, the underlying mechanisms remain unclear. This study was conducted to explore the effect of Mel on endoplasmic reticulum (ER) stress, Akt and MAPK cascades after renal warm I/R. Eighteen Wi...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2015/635172 |
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| author | Kaouther Hadj Ayed Tka Asma Mahfoudh Boussaid Mohamed Amine Zaouali Rym Kammoun Mohamed Bejaoui Sonia Ghoul Mazgar Joan Rosello Catafau Hassen Ben Abdennebi |
| author_facet | Kaouther Hadj Ayed Tka Asma Mahfoudh Boussaid Mohamed Amine Zaouali Rym Kammoun Mohamed Bejaoui Sonia Ghoul Mazgar Joan Rosello Catafau Hassen Ben Abdennebi |
| author_sort | Kaouther Hadj Ayed Tka |
| collection | DOAJ |
| description | Melatonin (Mel) is widely used to attenuate ischemia/reperfusion (I/R) injury in several organs. Nevertheless, the underlying mechanisms remain unclear. This study was conducted to explore the effect of Mel on endoplasmic reticulum (ER) stress, Akt and MAPK cascades after renal warm I/R. Eighteen Wistar rats were randomized into three groups: Sham, I/R, and Mel + I/R. The ischemia period was 60 min followed by 120 min of reperfusion. Mel (10 mg/kg) was administrated 30 min prior to ischemia. The creatinine clearance, MDA, LDH levels, and histopathological changes were evaluated. In addition, Western blot was performed to study ER stress and its downstream apoptosis as well as phosphorylation of Akt, GSK-3β, VDAC, ERK, and P38. Mel decreased cytolysis and lipid peroxidation and improved renal function and morphology compared to I/R group. Parallely, it significantly reduced the ER stress parameters including GRP 78, p-PERK, XBP 1, ATF 6, CHOP, and JNK. Simultaneously, p-Akt level was significantly enhanced and its target molecules GSK-3β and VDAC were inhibited. Furthermore, the ERK and P38 phosphorylation were evidently augmented after Mel administration in comparison to I/R group. In conclusion, Mel improves the recovery of renal function by decreasing ER stress and stimulating Akt pathway after renal I/R injury. |
| format | Article |
| id | doaj-art-d02fc02fa52a4cf9ba7393c9d1046acf |
| institution | DOAJ |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-d02fc02fa52a4cf9ba7393c9d1046acf2025-08-20T03:19:45ZengWileyAnalytical Cellular Pathology2210-71772210-71852015-01-01201510.1155/2015/635172635172Melatonin Modulates Endoplasmic Reticulum Stress and Akt/GSK3-Beta Signaling Pathway in a Rat Model of Renal Warm Ischemia ReperfusionKaouther Hadj Ayed Tka0Asma Mahfoudh Boussaid1Mohamed Amine Zaouali2Rym Kammoun3Mohamed Bejaoui4Sonia Ghoul Mazgar5Joan Rosello Catafau6Hassen Ben Abdennebi7Unit of Molecular Biology and Anthropology Applied to Development and Health (UR12ES11), Faculty of Pharmacy, University of Monastir, rue Avicenne, 5000 Monastir, TunisiaUnit of Molecular Biology and Anthropology Applied to Development and Health (UR12ES11), Faculty of Pharmacy, University of Monastir, rue Avicenne, 5000 Monastir, TunisiaUnit of Molecular Biology and Anthropology Applied to Development and Health (UR12ES11), Faculty of Pharmacy, University of Monastir, rue Avicenne, 5000 Monastir, TunisiaLaboratory of Histology and Embryology, Faculty of Dental Medicine, University of Monastir, rue Avicenne, 5000 Monastir, TunisiaUnit of Experimental Hepatic Ischemia-Reperfusion, Institute of Biomedical Investigations, Higher Council of Scientific Investigations, 08036 Barcelona, SpainLaboratory of Histology and Embryology, Faculty of Dental Medicine, University of Monastir, rue Avicenne, 5000 Monastir, TunisiaUnit of Experimental Hepatic Ischemia-Reperfusion, Institute of Biomedical Investigations, Higher Council of Scientific Investigations, 08036 Barcelona, SpainUnit of Molecular Biology and Anthropology Applied to Development and Health (UR12ES11), Faculty of Pharmacy, University of Monastir, rue Avicenne, 5000 Monastir, TunisiaMelatonin (Mel) is widely used to attenuate ischemia/reperfusion (I/R) injury in several organs. Nevertheless, the underlying mechanisms remain unclear. This study was conducted to explore the effect of Mel on endoplasmic reticulum (ER) stress, Akt and MAPK cascades after renal warm I/R. Eighteen Wistar rats were randomized into three groups: Sham, I/R, and Mel + I/R. The ischemia period was 60 min followed by 120 min of reperfusion. Mel (10 mg/kg) was administrated 30 min prior to ischemia. The creatinine clearance, MDA, LDH levels, and histopathological changes were evaluated. In addition, Western blot was performed to study ER stress and its downstream apoptosis as well as phosphorylation of Akt, GSK-3β, VDAC, ERK, and P38. Mel decreased cytolysis and lipid peroxidation and improved renal function and morphology compared to I/R group. Parallely, it significantly reduced the ER stress parameters including GRP 78, p-PERK, XBP 1, ATF 6, CHOP, and JNK. Simultaneously, p-Akt level was significantly enhanced and its target molecules GSK-3β and VDAC were inhibited. Furthermore, the ERK and P38 phosphorylation were evidently augmented after Mel administration in comparison to I/R group. In conclusion, Mel improves the recovery of renal function by decreasing ER stress and stimulating Akt pathway after renal I/R injury.http://dx.doi.org/10.1155/2015/635172 |
| spellingShingle | Kaouther Hadj Ayed Tka Asma Mahfoudh Boussaid Mohamed Amine Zaouali Rym Kammoun Mohamed Bejaoui Sonia Ghoul Mazgar Joan Rosello Catafau Hassen Ben Abdennebi Melatonin Modulates Endoplasmic Reticulum Stress and Akt/GSK3-Beta Signaling Pathway in a Rat Model of Renal Warm Ischemia Reperfusion Analytical Cellular Pathology |
| title | Melatonin Modulates Endoplasmic Reticulum Stress and Akt/GSK3-Beta Signaling Pathway in a Rat Model of Renal Warm Ischemia Reperfusion |
| title_full | Melatonin Modulates Endoplasmic Reticulum Stress and Akt/GSK3-Beta Signaling Pathway in a Rat Model of Renal Warm Ischemia Reperfusion |
| title_fullStr | Melatonin Modulates Endoplasmic Reticulum Stress and Akt/GSK3-Beta Signaling Pathway in a Rat Model of Renal Warm Ischemia Reperfusion |
| title_full_unstemmed | Melatonin Modulates Endoplasmic Reticulum Stress and Akt/GSK3-Beta Signaling Pathway in a Rat Model of Renal Warm Ischemia Reperfusion |
| title_short | Melatonin Modulates Endoplasmic Reticulum Stress and Akt/GSK3-Beta Signaling Pathway in a Rat Model of Renal Warm Ischemia Reperfusion |
| title_sort | melatonin modulates endoplasmic reticulum stress and akt gsk3 beta signaling pathway in a rat model of renal warm ischemia reperfusion |
| url | http://dx.doi.org/10.1155/2015/635172 |
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