SIRT1-mediated deacetylation of PGC1α attributes to the protection of curcumin against glutamate excitotoxicity in cortical neurons
- Department of Human Anatomy, Histology and Embryology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061 (China)
- Institute of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061 (China)
- Division of Neonatology, First Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061 (China)
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. - Highlights: • Curcumin attenuates glutamate induced cell death and apoptosis in cultured neurons. • Curcumin preserves mitochondrial function in the presence of glutamate. • Curcumin enhanced the expression of SIRT1 in the glutamate rich environment. • SIRT1-mediated deacetylation of PGC1α attributes to the neuroprotection of curcumin.
- OSTI ID:
- 22696615
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 478; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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