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LncRNA NEAT1 ameliorate ischemic stroke via promoting Mfn2 expression through binding to Nova and activates Sirt3

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Abstract

Background

Recent studies revealed that long non-coding RNAs (lncRNAs) have significant roles in regulating the pathogenesis of ischemia stroke, and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cell apoptosis. Aberrant expression of NEAT1 was found after the injury of ischemia-reperfusion, but the mechanism was not fully understood.

Methods

The expression of NEAT1 and Mfn2 were detected in BV-2 and N2a cell with or without OGD/R-induced by qRT-PCR. Inflammatory cytokines secretion was detected by enzyme-linked immunosorbent assay (ELISA). The oxidative stress was evaluated by the examination of ROS, MDA and SOD levels. Flow cytometry and apoptosis marker detection by western blot were performed to examined apoptosis.

Results

The expression of NEAT1 and Mfn2 were decreased in OGD/R-induced cell model. Overexpression of NEAT1 or Mfn2 reduced oxidative stress and apoptosis by OGD/R-induced in neuronal cells, while knockdown of Sirt3 reversed the protective effect of NEAT1 and Mfn2. NEAT1 stabilized Mfn2 mRNA via recruiting Nova. NEAT1 alleviates the oxidative stress and apoptosis by OGD/R-induced via activating Sirt3.

Conclusion

LncRNA NEAT1 stabilizes Mfn2 mRNA via recruiting Nova, therefore increase the expression of Mfn2 and alleviates ischemia-reperfusion induced oxidative stress and apoptosis via Mfn2/Sirt3 pathway.

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Abbreviations

I/R:

ischemia/reperfusion

lncRNA:

long non-coding RNA

siRNA:

small interfering RNA

qRT-PCR:

quantitative reverse-transcription polymerase chain reaction

ELISA:

Enzyme-Linked Immunosorbent Assay

TNF-α:

tumor necrosis factor-α

IL-1β:

interleukin-1β

IL-6:

interleukin-6

OGD/R:

oxygen-glucose deprivation/reoxygenation

IS:

ischemic stroke

MDA:

malondialdehyde

SOD:

superoxide dismutase

TBST:

Tris buffered saline Tween

PVDF:

polyvinylidene difluoride

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Acknowledgements

We would like to give our sincere gratitude to the reviewers for their constructive comments. This work was supported by Natural Science Foundation Youth Project of Hunan Province (project number 2020JJ5311).

Availability of Data and Material

All data generated or analyzed during this study are included in this article. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Funding

This work was supported by Natural Science Foundation Youth Project of Hunan Province (project number 2020JJ5311).

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Authors and Affiliations

  1. Departments of Neurology, Hunan Provincial People’s Hospital, The First-Affiliated Hospital of Hunan Normal University, No.89, Guhan Road, Changsha, 410016, Hunan Province, People’s Republic of China

    Zhi-Wen Zhou, Xiang Ren, Ai-Ping Li & Wen-Sheng Zhou

  2. Department of Rehabilitation Medicine, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410016, Hunan Province, People’s Republic of China

    Li-Jun Zheng

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  1. Zhi-Wen Zhou
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Contributions

ZWZ: Conceptualization; Writing-original draft; Methodology; Formal analysis;

XR: Supervision; Validation;

LJZ: Data curation; Resources;

APL: Investigation; Software; Visualization;

WSZ: Funding acquisition; Project administration; Writing-review & editing.

All authors have read and approved the final version of this manuscript to be published.

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Correspondence to Wen-Sheng Zhou.

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Zhou, ZW., Ren, X., Zheng, LJ. et al. LncRNA NEAT1 ameliorate ischemic stroke via promoting Mfn2 expression through binding to Nova and activates Sirt3. Metab Brain Dis 37, 653–664 (2022). https://doi.org/10.1007/s11011-021-00895-1

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