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

Authors Bu XS, Wu D, Lu XM, Yang L, Xu XY, Wang J, Tang JL

Received 30 November 2016

Accepted for publication 18 January 2017

Published 23 June 2017 Volume 2017:13 Pages 1633—1645

DOI https://doi.org/10.2147/NDT.S129081

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Prof. Dr. Roumen Kirov

Peer reviewer comments 3

Editor who approved publication: Professor Wai Kwong Tang


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

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