Open Access

SIRT3 expression alleviates microglia activation‑induced dopaminergic neuron injury through the mitochondrial pathway

  • Authors:
    • De-Qi Jiang
    • Qing-Min Zang
    • Li-Lin Jiang
    • Cheng-Shu Lu
    • Shi-Hua Zhao
    • Lan-Cheng Xu
  • View Affiliations

  • Published online on: September 7, 2022     https://doi.org/10.3892/etm.2022.11598
  • Article Number: 662
  • Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The mitochondrial protein sirtuin 3 (SIRT3) can counteract cell damage caused by oxidative stress and inflammation, and contribute to cell survival primarily by improving mitochondrial function. However, the effects of SIRT3 in dopaminergic neuronal cells (DACs) remain unclear. In our previous studies, microglia activation‑associated cytotoxicity was observed to promote the apoptosis of DACs, along with the decrease of SIRT3 expression. The aim of the present study was to explore the potential neuroprotective effect of SIRT3 expression against dopaminergic neuron injury caused by microglia activation, and clarify its possible mechanisms. SIRT3 overexpression in DACs reduced the production of intracellular reactive oxygen species (ROS), cell apoptosis rate, mitochondrial membrane potential (ΔΨm) depolarization, opening of mitochondrial permeability transition pore (mPTP) and cyclophilin D (CypD) protein level, and promoted cell cycle progression. However, SIRT3 siRNA‑mediated knockdown further aggravated microglia activation‑mediated cytotoxicity, including ROS accumulation, increased cell apoptosis and mPTP opening, elevated the CypD level, enhanced mitochondrial ΔΨm depolarization, concomitant to cell cycle arrest at G0/G1 phase. The mechanisms of SIRT3 mitigated microglia activation‑induced DAC dysfunction, which included decreased mPTP opening and Bax/Bcl‑2 ratio, inhibition of mitochondrial cytochrome c release to the cytoplasm, reduced caspase‑3/9 activity, increased LC3II/LC3I and beclin‑1 protein expression levels, and decreased nucleotide‑binding oligomerization domain, leucine rich repeat and pyrin domain‑containing protein 3 (NLRP3), caspase‑1, IL‑1β and IL‑18 protein expression. In conclusion, these results indicated that SIRT3 expression attenuated cell damage caused by microglia activation through the mitochondrial apoptosis pathway in DACs. The mitophagy‑NLRP3 inflammasome pathway may also be associated with this neuroprotection. These findings may provide new intervention targets for the survival of dopaminergic neurons and the prevention and treatment of Parkinson's disease.
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November-2022
Volume 24 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Copy and paste a formatted citation
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Spandidos Publications style
Jiang D, Zang Q, Jiang L, Lu C, Zhao S and Xu L: SIRT3 expression alleviates microglia activation‑induced dopaminergic neuron injury through the mitochondrial pathway. Exp Ther Med 24: 662, 2022
APA
Jiang, D., Zang, Q., Jiang, L., Lu, C., Zhao, S., & Xu, L. (2022). SIRT3 expression alleviates microglia activation‑induced dopaminergic neuron injury through the mitochondrial pathway. Experimental and Therapeutic Medicine, 24, 662. https://doi.org/10.3892/etm.2022.11598
MLA
Jiang, D., Zang, Q., Jiang, L., Lu, C., Zhao, S., Xu, L."SIRT3 expression alleviates microglia activation‑induced dopaminergic neuron injury through the mitochondrial pathway". Experimental and Therapeutic Medicine 24.5 (2022): 662.
Chicago
Jiang, D., Zang, Q., Jiang, L., Lu, C., Zhao, S., Xu, L."SIRT3 expression alleviates microglia activation‑induced dopaminergic neuron injury through the mitochondrial pathway". Experimental and Therapeutic Medicine 24, no. 5 (2022): 662. https://doi.org/10.3892/etm.2022.11598