title: SIRT1-mediated deacetylation of PGC1α attributes to the protection of curcumin against glutamate excitotoxicity in cortical neurons.
abstract: It is widely accepted that accumulation of extracellular glutamate mediates neuronal injuries in a number of neurological disorders via binding glutamate receptors. However, usage of the glutamate receptor antagonists aimed to prevent glutamate excitotoxicity is still controversial. As a polyphenol natural product, curcumin, has been implied multiple bioactivities. In this study, we explored whether the silent information regulator 1 (SIRT1)-peroxisome proliferator-activated receptor-coactivator 1α (PGC1α) pathway participated in the protection of curcumin against glutamate excitotoxicity. The cultured primary cortical neurons were treated with glutamate to set up a neuronal excitotoxicity model. The MTT and TUNEL methods were employed to measure cell viability and apoptosis, respectively. The mitochondrial function, the expression levels of SIRT1, PGC1α and acetylated PGC1α (ac-PGC1α) were measured to explore the mechanism of curcumin against glutamate excitotoxicity. The results showed that glutamate significantly induced cell death and apoptosis, which was blocked by pretreatment with curcumin. Meanwhile, curcumin preserved mitochondrial function, increased the expression level of SIRT1 and reduced the level of ac-PGC1α in the presence of glutamate. These results suggest that SIRT1-mediated deacetylation of PGC1α attributes to the neuroprotection of curcumin against glutamate excitotoxicity.
authors: Department of Human Anatomy, Histology and Embryology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, PR China. Electronic address: jianing@mail.xjtu.edu.cn.
authors: Ning
authors: N
authors: Jia
authors: Institute of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, PR China. Electronic address: qinrusun@mail.xjtu.edu.cn.
authors: Qinru
authors: Q
authors: Sun
authors: Division of Neonatology, First Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, PR China.
authors: Qian
authors: Q
authors: Su
authors: Department of Human Anatomy, Histology and Embryology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, PR China.
authors: Guomin
authors: G
authors: Chen
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology*; D003474:Curcumin / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000378:metabolism; D018698:Glutamic Acid / Q000633:toxicity*; D042541:Intracellular Space / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009284:Naphthols / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000066829:Neuroprotection / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D001549:Benzamides; D009284:Naphthols; D018696:Neuroprotective Agents; D009498:Neurotoxins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D017382:Reactive Oxygen Species; C439060:sirtinol; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D056564:Sirtuin 1; D003474:Curcumin; D002118:Calcium
keywords: Cultured neuron; Curcumin; Glutamate excitotoxicity; PGC1α; SIRT1