Rapid modulation of the silent information regulator 1 by melatonin after hypoxia-ischemia in the neonatal rat brain
Autor: | Giulia Riparini, Giuseppe Buonocore, Walter Balduini, Silvia Carloni |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
medicine.medical_specialty melatonin Mitochondrion Biology Neuroprotection Brain Ischemia Melatonin Rats Sprague-Dawley 03 medical and health sciences SIRT1 Endocrinology Sirtuin 1 Pregnancy Internal medicine Glial Fibrillary Acidic Protein medicine Animals Progenitor cell Neurons Cell Death Intrinsic apoptosis Autophagy hypoxia-ischemia 030104 developmental biology Animals Newborn Apoptosis SIRT1 melatonin hypoxia-ischemia neuroprotection Female neuroprotection Tumor Suppressor Protein p53 Cell activation silent information regulator 1 hormones hormone substitutes and hormone antagonists medicine.drug |
Popis: | Increasing evidence indicates that melatonin possesses protective effects toward different kinds of damage in various organs, including the brain. In a neonatal model of hypoxia-ischemia (HI), melatonin was neuroprotective and preserved the expression of the silent information regulator 1 (SIRT1) 24 hours after the insult. This study aimed to gain more insight into the role of SIRT1 in the protective effect of melatonin after HI by studying the early (1 hour) modulation of SIRT1 and its downstream targets, and the consequences on necrosis, apoptosis, autophagy, and glial cell activation. We found that melatonin administered 5 minutes after the ischemic insult significantly reduced necrotic cell death assessed 1 hour after its administration. In parallel, we found a reduced activation of the early phases of intrinsic apoptosis, detected by reduced BAX translocation to the mitochondria and preservation of the mitochondrial expression of cytochrome C, indicating a reduced outer mitochondrial membrane permeabilization in the melatonin-treated ischemic animals. These effects were concomitant to increased expression and activity of SIRT1, reduced expression and acetylation of p53, and increased autophagy activation. Melatonin also reduced HI-induced glial cells activation. SIRT1 was expressed in neurons after HI and melatonin but not in reactive glial cells expressing GFAP. Colocalization between SIRT1 and GFAP was found in some cells in control conditions. In summary, our results provide more insight into the connection between SIRT1 and melatonin in neuroprotection. The possibility that melatonin-induced SIRT1 activity might contribute to differentiate neuronal progenitor cells during the neurodegenerative process needs to be further investigated. |
Databáze: | OpenAIRE |
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