Dataset Information

Nrf2 Inhibits the Progression of Parkinson's Disease by Upregulating AABR07032261.5 to Repress Pyroptosis.

ABSTRACT:

Objective

Parkinson's disease (PD) is associated with dysregulated neural cell death, such as pyroptosis, but its regulatory mechanisms are poorly understood. This study investigated roles of nuclear factor E2-related factor 2 (Nrf2) in regulating pyroptosis and PD development.

Methods

Cellular and rat PD models established by 6-OHDA exposure were subjected to Nrf2 overexpression. Neurobehavioral functions were assessed by the traction test, Morris Water Maze, and open field test. Cell proliferation was analyzed by MTS assay, while flow cytometry was applied to quantify levels of reactive oxygen species (ROS) and apoptosis. Nissl bodies in rat brains were detected by Nissl staining, and cell apoptosis in brain tissues was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling. Differential expression of lncRNA and mRNA was characterized by deep sequencing.

Results

A cellular PD model was successfully established by inducing PC12 cell differentiation with nerve growth factor-β and exposing differentiated cells to 6-OHDA. Cells exhibited significantly increased ROS levels, enhanced pyroptosis, and inhibited Nrf2 phosphorylation. The rat PD model exhibited impaired muscle strength, increased pyroptosis, and repressed Nrf2 phosphorylation. Nrf2 overexpression effectively repressed pyroptosis in both cellular and rat PD models. Marked alterations of lncRNA and mRNA profiles were induced by Nrf2 overexpression in the cellular PD model, which involved multiple signaling pathways. Silencing of the lncRNA AABR07032261.5 significantly promoted pyroptosis in the cellular PD model.

Conclusion

Nrf2 suppressed PD pathogenesis in cellular and animal models by promoting AABR07032261.5, which repressed pyroptosis.

SUBMITTER: Zhong Y

PROVIDER: S-EPMC8818975 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Nrf2 Inhibits the Progression of Parkinson's Disease by Upregulating AABR07032261.5 to Repress Pyroptosis.

Zhong Yunxiao Y Cai Xiaodong X Ding Li L Liao Jinchi J Liu Xu X Huang Yiying Y Chen Xiaohong X Long Ling L

Journal of inflammation research 20220202

<h4>Objective</h4>Parkinson's disease (PD) is associated with dysregulated neural cell death, such as pyroptosis, but its regulatory mechanisms are poorly understood. This study investigated roles of nuclear factor E2-related factor 2 (Nrf2) in regulating pyroptosis and PD development.<h4>Methods</h4>Cellular and rat PD models established by 6-OHDA exposure were subjected to Nrf2 overexpression. Neurobehavioral functions were assessed by the traction test, Morris Water Maze, and open field test. ...[more]

PMID: 35140498

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Project description:BackgroundGlioma is the most common and aggressive primary brain tumor in adults. Proteasome 26S subunit, non-ATPase 12 (PSMD12), an important subunit in the 26S proteasome, is known to be involved in the growth and apoptosis of breast cancer cells. However, its exact function and underlying molecular mechanisms in glioma remain unknown.MethodsPSMD12 expression was detected in glioma tissue specimens by immunohistochemistry (IHC) and TCGA database. Overexpression and down-regulation of PSMD12 and Nrf2 were induced in glioma cell lines, and CCK-8 and Transwell assays were used to detect cell proliferation and invasion evaluation, respectively. Xenograft model was used to observe the effect of knockdown of PSMD12 on tumor growth. Immunohistochemical assays and TCGA database were conducted to reveal the relationships between PSMD12 expression and Nrf2. Finally, Western blot and related biological function experiments were used to explore the mechanism of PSMD12 regulating the glioma progression and Nrf2.ResultsWe revealed that PSMD12 is upregulated in glioma, especially in high-grade glioma, by analyzing bioinformatics data and clinical specimens. PSMD12 upregulation was associated with poor prognosis in glioma patients. Knockdown of PSMD12 inhibited the growth of glioma cells in vitro and in vivo and decreased their invasion ability, whereas PSMD12 overexpression had the opposite effect. Mechanistic analysis revealed that PSMD12 increased the expression of nuclear factor E2-related factor 2 (Nrf2), which functions as a tumor promoter in the development of glioma. Similar to PSMD12, Nrf2, which exhibited a strong positive correlation with PSMD12, was abnormally elevated in glioma tissues and contributed to worse overall survival (OS). Nrf2 overexpression reversed the inhibitory effects induced by PSMD12 knockdown. Finally, PSMD12 enhanced the proliferation and invasion of glioma cells via Akt signaling-mediated Nrf2 expression.ConclusionsThese results suggest that PSMD12 is considered to be a crucial regulator of the development and progression of glioma and may serve as a potential biomarker or therapeutic target for the treatment of glioma.

Dataset Information

Nrf2 Inhibits the Progression of Parkinson's Disease by Upregulating AABR07032261.5 to Repress Pyroptosis.

Objective

Methods

Results

Conclusion

Publications

Nrf2 Inhibits the Progression of Parkinson's Disease by Upregulating AABR07032261.5 to Repress Pyroptosis.

Similar Datasets

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