Role of SIRT1/PGC-1α in mitochondrial oxidative stress in autistic spectrum disorder

Role of SIRT1/PGC-1α in mitochondrial oxidative stress in autistic spectrum disorder

Xiaosong Bu, De Wu, Xiaomei Lu, Li Yang, Xiaoyan Xu, Juan Wang, Jiulai Tang Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China Abstract: Autistic spectrum disorder (ASD) is a neurodevelopmental disorder and has a high pr...

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Autores principales: Bu XS, Wu D, Lu XM, Yang L, Xu XY, Wang J, Tang JL
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2017
Materias:
Autistic spectrum disorder
PGC-1α
SIRT1
mitochondria
oxidative stress
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Acceso en línea:https://doaj.org/article/bcaa8ca200734bd188b2a415cd027133
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spelling oai:doaj.org-article:bcaa8ca200734bd188b2a415cd0271332021-12-02T01:43:38ZRole of SIRT1/PGC-1α in mitochondrial oxidative stress in autistic spectrum disorder1178-2021https://doaj.org/article/bcaa8ca200734bd188b2a415cd0271332017-06-01T00:00:00Zhttps://www.dovepress.com/role-of-sirt1pgc-1alpha-in-mitochondrial-oxidative-stress-in-autistic--peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Xiaosong Bu, De Wu, Xiaomei Lu, Li Yang, Xiaoyan Xu, Juan Wang, Jiulai Tang Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China Abstract: Autistic spectrum disorder (ASD) is a neurodevelopmental disorder and has a high prevalence in children. Recently, mitochondrial oxidative stress has been proposed to be associated with ASD. Besides, SIRT1/PGC-1α signaling plays an important role in combating oxidative stress. In this study, we sought to determine the role of SIRT1/PGC-1α signaling in the ASD lymphoblastoid cell lines (LCLs). In this study, the mRNA and protein expressions of SIRT1/PGC-1α axis genes were assessed in 35 children with ASD and 35 healthy controls (matched for age, gender, and IQ). An immortalized LCL was established by transforming lymphocytes with Epstein–Barr virus. Next, we used ASD LCLs and control LCLs to detect SIRT1/PGC-1α axis genes expression and oxidative damage. Finally, the effect of overexpression of PGC-1α on oxidative injury in the ASD LCLs was determined. SIRT1/PGC-1α axis genes expression was downregulated at RNA and protein levels in ASD patients and LCLs. Besides, the translocation of cytochrome c and DIABLO from mitochondria to the cytosol was found in the ASD LCLs. Moreover, the intracellular reactive oxygen species (ROS) and mitochondrial ROS and cell apoptosis were increased in the ASD LCLs. However, overexpression of PGC-1α upregulated the SIRT1/PGC-1α axis genes expression and reduced cytochrome c and DIABLO release in the ASD LCLs. Also, overexpression of PGC-1α reduced the ROS generation and cell apoptosis in the ASD LCLs. Overexpression of PGC-1α could reduce the oxidative injury in the ASD LCLs, and PGC-1α may act as a target for treatment. Keywords: autistic spectrum disorder, PGC-1α, SIRT1, mitochondria, oxidative stressBu XSWu DLu XMYang LXu XYWang JTang JLDove Medical PressarticleAutistic spectrum disorderPGC-1αSIRT1mitochondriaoxidative stressNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 13, Pp 1633-1645 (2017)
institution DOAJ
collection DOAJ
language EN
topic Autistic spectrum disorder
PGC-1α
SIRT1
mitochondria
oxidative stress
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
spellingShingle Autistic spectrum disorder
PGC-1α
SIRT1
mitochondria
oxidative stress
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Bu XS
Wu D
Lu XM
Yang L
Xu XY
Wang J
Tang JL
Role of SIRT1/PGC-1α in mitochondrial oxidative stress in autistic spectrum disorder
description Xiaosong Bu, De Wu, Xiaomei Lu, Li Yang, Xiaoyan Xu, Juan Wang, Jiulai Tang Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China Abstract: Autistic spectrum disorder (ASD) is a neurodevelopmental disorder and has a high prevalence in children. Recently, mitochondrial oxidative stress has been proposed to be associated with ASD. Besides, SIRT1/PGC-1α signaling plays an important role in combating oxidative stress. In this study, we sought to determine the role of SIRT1/PGC-1α signaling in the ASD lymphoblastoid cell lines (LCLs). In this study, the mRNA and protein expressions of SIRT1/PGC-1α axis genes were assessed in 35 children with ASD and 35 healthy controls (matched for age, gender, and IQ). An immortalized LCL was established by transforming lymphocytes with Epstein–Barr virus. Next, we used ASD LCLs and control LCLs to detect SIRT1/PGC-1α axis genes expression and oxidative damage. Finally, the effect of overexpression of PGC-1α on oxidative injury in the ASD LCLs was determined. SIRT1/PGC-1α axis genes expression was downregulated at RNA and protein levels in ASD patients and LCLs. Besides, the translocation of cytochrome c and DIABLO from mitochondria to the cytosol was found in the ASD LCLs. Moreover, the intracellular reactive oxygen species (ROS) and mitochondrial ROS and cell apoptosis were increased in the ASD LCLs. However, overexpression of PGC-1α upregulated the SIRT1/PGC-1α axis genes expression and reduced cytochrome c and DIABLO release in the ASD LCLs. Also, overexpression of PGC-1α reduced the ROS generation and cell apoptosis in the ASD LCLs. Overexpression of PGC-1α could reduce the oxidative injury in the ASD LCLs, and PGC-1α may act as a target for treatment. Keywords: autistic spectrum disorder, PGC-1α, SIRT1, mitochondria, oxidative stress
format article
author Bu XS
Wu D
Lu XM
Yang L
Xu XY
Wang J
Tang JL
author_facet Bu XS
Wu D
Lu XM
Yang L
Xu XY
Wang J
Tang JL
author_sort Bu XS
title Role of SIRT1/PGC-1α in mitochondrial oxidative stress in autistic spectrum disorder
title_short Role of SIRT1/PGC-1α in mitochondrial oxidative stress in autistic spectrum disorder
title_full Role of SIRT1/PGC-1α in mitochondrial oxidative stress in autistic spectrum disorder
title_fullStr Role of SIRT1/PGC-1α in mitochondrial oxidative stress in autistic spectrum disorder
title_full_unstemmed Role of SIRT1/PGC-1α in mitochondrial oxidative stress in autistic spectrum disorder
title_sort role of sirt1/pgc-1α in mitochondrial oxidative stress in autistic spectrum disorder
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/bcaa8ca200734bd188b2a415cd027133
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