Sirtuin 1 Regulates Mitochondrial Biogenesis and Provides an Endogenous Neuroprotective Mechanism Against Seizure-Induced Neuronal Cell Death in the Hippocampus Following Status Epilepticus

Department of Neurology, Kaohsiung Medical University Hospital and School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan

⁵

Department of Biological Science, National Sun Yat-Sen University, Kaohsiung City 80424, Taiwan

⁶

Department of Neurology, Mackay Memorial Hospital and Mackay Medical College, Taipei 10449, Taiwan

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2019, 20(14), 3588; https://doi.org/10.3390/ijms20143588

Received: 28 June 2019 / Revised: 21 July 2019 / Accepted: 22 July 2019 / Published: 23 July 2019

(This article belongs to the Special Issue Neuroprotective Strategies 2019)

View Full-Text Download PDF

Browse Figures

Review Reports Citation Export

Abstract

Status epilepticus may decrease mitochondrial biogenesis, resulting in neuronal cell death occurring in the hippocampus. Sirtuin 1 (SIRT1) functionally interacts with peroxisome proliferator-activated receptors and γ coactivator 1α (PGC-1α), which play a crucial role in the regulation of mitochondrial biogenesis. In Sprague-Dawley rats, kainic acid was microinjected unilaterally into the hippocampal CA3 subfield to induce bilateral seizure activity. SIRT1, PGC-1α, and other key proteins involving mitochondrial biogenesis and the amount of mitochondrial DNA were investigated. SIRT1 antisense oligodeoxynucleotide was used to evaluate the relationship between SIRT1 and mitochondrial biogenesis, as well as the mitochondrial function, oxidative stress, and neuronal cell survival. Increased SIRT1, PGC-1α, and mitochondrial biogenesis machinery were found in the hippocampus following experimental status epilepticus. Downregulation of SIRT1 decreased PGC-1α expression and mitochondrial biogenesis machinery, increased Complex I dysfunction, augmented the level of oxidized proteins, raised activated caspase-3 expression, and promoted neuronal cell damage in the hippocampus. The results suggest that the SIRT1 signaling pathway may play a pivotal role in mitochondrial biogenesis, and could be considered an endogenous neuroprotective mechanism counteracting seizure-induced neuronal cell damage following status epilepticus. View Full-Text

Keywords: SIRT1; PGC-1α; mitochondrial biogenesis; status epilepticus; hippocampus

▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Share and Cite

MDPI and ACS Style

Chuang, Y.-C.; Chen, S.-D.; Jou, S.-B.; Lin, T.-K.; Chen, S.-F.; Chen, N.-C.; Hsu, C.-Y. Sirtuin 1 Regulates Mitochondrial Biogenesis and Provides an Endogenous Neuroprotective Mechanism Against Seizure-Induced Neuronal Cell Death in the Hippocampus Following Status Epilepticus. Int. J. Mol. Sci. 2019, 20, 3588. https://doi.org/10.3390/ijms20143588

AMA Style

Chuang Y-C, Chen S-D, Jou S-B, Lin T-K, Chen S-F, Chen N-C, Hsu C-Y. Sirtuin 1 Regulates Mitochondrial Biogenesis and Provides an Endogenous Neuroprotective Mechanism Against Seizure-Induced Neuronal Cell Death in the Hippocampus Following Status Epilepticus. International Journal of Molecular Sciences. 2019; 20(14):3588. https://doi.org/10.3390/ijms20143588

Chicago/Turabian Style

Chuang, Yao-Chung, Shang-Der Chen, Shuo-Bin Jou, Tsu-Kung Lin, Shu-Fang Chen, Nai-Ching Chen, and Chung-Yao Hsu. 2019. "Sirtuin 1 Regulates Mitochondrial Biogenesis and Provides an Endogenous Neuroprotective Mechanism Against Seizure-Induced Neuronal Cell Death in the Hippocampus Following Status Epilepticus" International Journal of Molecular Sciences 20, no. 14: 3588. https://doi.org/10.3390/ijms20143588

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

Sirtuin 1 Regulates Mitochondrial Biogenesis and Provides an Endogenous Neuroprotective Mechanism Against Seizure-Induced Neuronal Cell Death in the Hippocampus Following Status Epilepticus

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI