UCP2 silencing aggravates mitochondrial dysfunction in astrocytes under septic conditions

Peng,Wanwan; Huang,Jinda; Zheng,Yijun; Ding,Yue; Li,Sitao; Zhang,Junliang; Lyu,Juanjuan; Zeng,Qiyi

doi:10.3892/mmr.2019.10721

UCP2 silencing aggravates mitochondrial dysfunction in astrocytes under septic conditions

Authors:
- Wanwan Peng
- Jinda Huang
- Yijun Zheng
- Yue Ding
- Sitao Li
- Junliang Zhang
- Juanjuan Lyu
- Qiyi Zeng
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Affiliations: Department of Pediatrics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China, Pediatric Intensive Care Unit, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong 510623, P.R. China, Department of Neonatology, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong 510623, P.R. China, Department of Pediatrics, The Sixth Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510655, P.R. China, Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: October 2, 2019 https://doi.org/10.3892/mmr.2019.10721
Pages: 4459-4466
Copyright: © Peng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Uncoupling protein 2 (UCP2) plays a positive role in sepsis. However, the role of UCP2 in experimental sepsis in astrocytes remains unknown. The present study was designed to determine whether UCP2 has a protective effect in an experimental sepsis model in astrocytes asnd to clarify the mechanisms responsible for its neuroprotective effects after sepsis. An experimental astrocyte model mimicking sepsis‑induced brain injury was established using lipopolysaccharide (LPS) and interferon (IFN)‑γ. Additionally, UCP2 knockdown in astrocytes was achieved by adenovirus transfection. Tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β activity, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS), and adenosine triphosphate (ATP) levels were assessed. The mitochondrial ultrastructure was evaluated, and the expression of UCP2 was determined by western blotting. LPS with IFN‑γ co‑stimulation increased the mRNA and protein expression levels of UCP2 in astrocytes, damaged the mitochondrial structure, and accelerated the release of TNF‑α and IL‑1β, resulting in a decrease in the MMP, and the excessive generation of ROS. Moreover, sepsis also caused a reduction in ATP production. The knockdown of UCP2 exacerbated astrocyte injury and mitochondrial impairment. In conclusion, both the function and morphology of mitochondria were damaged in an experimental model of sepsis in astrocytes, and knockdown of UCP2 using shRNA exacerbated this impairment, suggesting that UCP2 has a positive effect on astrocytes as determined in an experimental sepsis model.

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