Autophagy induction by SIRT6 is involved in oxidative stress-induced neuronal damage
Open Access
- 16 March 2016
- journal article
- research article
- Published by Oxford University Press (OUP) in Protein & Cell
- Vol. 7 (4), 281-290
- https://doi.org/10.1007/s13238-016-0257-6
Abstract
SIRT6 is a NAD+-dependent histone deacetylase and has been implicated in the regulation of genomic stability, DNA repair, metabolic homeostasis and several diseases. The effect of SIRT6 in cerebral ischemia and oxygen/glucose deprivation (OGD) has been reported, however the role of SIRT6 in oxidative stress damage remains unclear. Here we used SH-SY5Y neuronal cells and found that overexpression of SIRT6 led to decreased cell viability and increased necrotic cell death and reactive oxygen species (ROS) production under oxidative stress. Mechanistic study revealed that SIRT6 induced autophagy via attenuation of AKT signaling and treatment with autophagy inhibitor 3-MA or knockdown of autophagy-related protein Atg5 rescued H2O2-induced neuronal injury. Conversely, SIRT6 inhibition suppressed autophagy and reduced oxidative stress-induced neuronal damage. These results suggest that SIRT6 might be a potential therapeutic target for neuroprotection.Keywords
This publication has 36 references indexed in Scilit:
- Biochemical Characterization of Sirtuin 6 in the Brain and Its Involvement in Oxidative Stress ResponseNeurochemical Research, 2014
- Oxidative stress and autophagy: the clash between damage and metabolic needsCell Death & Differentiation, 2014
- Activation of the Protein Deacetylase SIRT6 by Long-chain Fatty Acids and Widespread Deacylation by Mammalian SirtuinsPublished by Elsevier BV ,2013
- Adiponectin Modulates Oxidative Stress-Induced Autophagy in CardiomyocytesPLOS ONE, 2013
- Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicityAutophagy, 2013
- Suppression of Acquired Docetaxel Resistance in Prostate Cancer through Depletion of Notch- and Hedgehog-Dependent Tumor-Initiating CellsCancer Cell, 2012
- Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012Cell Death & Differentiation, 2011
- miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signalingProceedings of the National Academy of Sciences of the United States of America, 2011
- Ras is involved in the negative control of autophagy through the class I PI3-kinaseOncogene, 2004
- The Tumor Suppressor PTEN Positively Regulates Macroautophagy by Inhibiting the Phosphatidylinositol 3-Kinase/Protein Kinase B PathwayPublished by Elsevier BV ,2001