Sirtuin 1 activation enhances the PGC-1α/mitochondrial antioxidant system pathway in status epilepticus

Wang,Sheng-Jun; Zhao,Xiu-He; Chen,Wen; Bo,Ning; Wang,Xian-Jin; Chi,Zhao-Fu; Wu,Wei

doi:10.3892/mmr.2014.2724

Sirtuin 1 activation enhances the PGC-1α/mitochondrial antioxidant system pathway in status epilepticus

Authors:
- Sheng-Jun Wang
- Xiu-He Zhao
- Wen Chen
- Ning Bo
- Xian-Jin Wang
- Zhao-Fu Chi
- Wei Wu
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Affiliations: Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Neurology, Jinan Central Hospital, Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China, Clinical Laboratory, People's Hospital of Shenzhen, Guangdong 518020, P.R. China, Department of Neurology, Shandong Ankang Hospital, Jining, Shandong 272051, P.R. China
Published online on: October 21, 2014 https://doi.org/10.3892/mmr.2014.2724
Pages: 521-526

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Abstract

Sirtuin 1 (SIRT1) regulates numerous neuronal processes, including metabolism, antioxidation and aging, through activation of peroxisome proliferator-activated receptor coactivator 1-α (PGC-1α), an upstream regulator of mitochondrial biogenesis and function. However, the role of SIRT1 in the oxidative stress induced by seizures has yet to be elucidated. The present study aimed to investigate whether SIRT1 was involved in the activation of the PGC-1α/mitochondrial antioxidant system following status epilepticus (SE) in rats. The data demonstrated that SIRT1 expression and activity were enhanced in the rat hippocampus following SE. SIRT1 inhibition effectively blocked the SE-associated increase in PGC-1α and mitochondrial antioxidant enzymes, including superoxide dismutase 2 (SOD2) and uncoupling protein 2 (UCP2). Additionally, it was also demonstrated that the activation of SIRT1 enhanced mitochondrial electron transport chain complex I activity and increased ATP content. In conclusion, the present results suggest that SIRT1 activation may alleviate mitochondrial oxidative stress induced by seizures partially via PGC-1α signaling.

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