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SIRT1/PGC-1α Signaling Promotes Mitochondrial Functional Recovery and Reduces Apoptosis after Intracerebral Hemorrhage in Rats

Silent information regulator 1 (SIRT1) exerts neuroprotection in many neurodegenerative diseases. However, it is not clear if SIRT1 has protective effects after intracerebral hemorrhage (ICH)-induced brain injury in rats. Thus, our goal was to examine the influence of SIRT1 on ICH injuries and any u...

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Autores principales: Zhou, Yang, Wang, Shaohua, Li, Yixin, Yu, Shanshan, Zhao, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767311/
https://www.ncbi.nlm.nih.gov/pubmed/29375306
http://dx.doi.org/10.3389/fnmol.2017.00443
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author Zhou, Yang
Wang, Shaohua
Li, Yixin
Yu, Shanshan
Zhao, Yong
author_facet Zhou, Yang
Wang, Shaohua
Li, Yixin
Yu, Shanshan
Zhao, Yong
author_sort Zhou, Yang
collection PubMed
description Silent information regulator 1 (SIRT1) exerts neuroprotection in many neurodegenerative diseases. However, it is not clear if SIRT1 has protective effects after intracerebral hemorrhage (ICH)-induced brain injury in rats. Thus, our goal was to examine the influence of SIRT1 on ICH injuries and any underlying mechanisms of this influence. Brain injury was induced by autologous arterial blood (60 μL) injection into rat brains, and data show that activation of SIRT1 with SRT1720 (5 mg/kg) restored nuclear SIRT1, deacetylation of PGC-1α, and mitochondrial biogenesis and decreased mortality, behavioral deficits, and brain water content without significant changes in phosphorylated AMP-activated protein kinase (pAMPK) induced by ICH. Activation of SIRT1 with SRT1720 also restored mitochondrial electron transport chain proteins and decreased apoptotic proteins in ICH; however, these changes were reversed after ICH. In contrast, treatment with PGC-1α siRNA yielded opposite effects. To explore the protective effects of SIRT1 after ICH, siRNAs were used to knockdown SIRT1. Treatment with SIRT1 siRNA increased mortality, behavioral deficits, brain water content, mitochondrial dysfunction, and neurocyte apoptosis after ICH. Thus, activation of SIRT1 promotes recovery of mitochondrial protein and function by increasing mitochondrial biogenesis and reduces apoptosis after ICH via the PGC-1α mitochondrial pathway. These data may suggest a new therapeutic approach for ICH injuries.
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spelling pubmed-57673112018-01-26 SIRT1/PGC-1α Signaling Promotes Mitochondrial Functional Recovery and Reduces Apoptosis after Intracerebral Hemorrhage in Rats Zhou, Yang Wang, Shaohua Li, Yixin Yu, Shanshan Zhao, Yong Front Mol Neurosci Neuroscience Silent information regulator 1 (SIRT1) exerts neuroprotection in many neurodegenerative diseases. However, it is not clear if SIRT1 has protective effects after intracerebral hemorrhage (ICH)-induced brain injury in rats. Thus, our goal was to examine the influence of SIRT1 on ICH injuries and any underlying mechanisms of this influence. Brain injury was induced by autologous arterial blood (60 μL) injection into rat brains, and data show that activation of SIRT1 with SRT1720 (5 mg/kg) restored nuclear SIRT1, deacetylation of PGC-1α, and mitochondrial biogenesis and decreased mortality, behavioral deficits, and brain water content without significant changes in phosphorylated AMP-activated protein kinase (pAMPK) induced by ICH. Activation of SIRT1 with SRT1720 also restored mitochondrial electron transport chain proteins and decreased apoptotic proteins in ICH; however, these changes were reversed after ICH. In contrast, treatment with PGC-1α siRNA yielded opposite effects. To explore the protective effects of SIRT1 after ICH, siRNAs were used to knockdown SIRT1. Treatment with SIRT1 siRNA increased mortality, behavioral deficits, brain water content, mitochondrial dysfunction, and neurocyte apoptosis after ICH. Thus, activation of SIRT1 promotes recovery of mitochondrial protein and function by increasing mitochondrial biogenesis and reduces apoptosis after ICH via the PGC-1α mitochondrial pathway. These data may suggest a new therapeutic approach for ICH injuries. Frontiers Media S.A. 2018-01-09 /pmc/articles/PMC5767311/ /pubmed/29375306 http://dx.doi.org/10.3389/fnmol.2017.00443 Text en Copyright © 2018 Zhou, Wang, Li, Yu and Zhao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Zhou, Yang
Wang, Shaohua
Li, Yixin
Yu, Shanshan
Zhao, Yong
SIRT1/PGC-1α Signaling Promotes Mitochondrial Functional Recovery and Reduces Apoptosis after Intracerebral Hemorrhage in Rats
title SIRT1/PGC-1α Signaling Promotes Mitochondrial Functional Recovery and Reduces Apoptosis after Intracerebral Hemorrhage in Rats
title_full SIRT1/PGC-1α Signaling Promotes Mitochondrial Functional Recovery and Reduces Apoptosis after Intracerebral Hemorrhage in Rats
title_fullStr SIRT1/PGC-1α Signaling Promotes Mitochondrial Functional Recovery and Reduces Apoptosis after Intracerebral Hemorrhage in Rats
title_full_unstemmed SIRT1/PGC-1α Signaling Promotes Mitochondrial Functional Recovery and Reduces Apoptosis after Intracerebral Hemorrhage in Rats
title_short SIRT1/PGC-1α Signaling Promotes Mitochondrial Functional Recovery and Reduces Apoptosis after Intracerebral Hemorrhage in Rats
title_sort sirt1/pgc-1α signaling promotes mitochondrial functional recovery and reduces apoptosis after intracerebral hemorrhage in rats
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767311/
https://www.ncbi.nlm.nih.gov/pubmed/29375306
http://dx.doi.org/10.3389/fnmol.2017.00443
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