HMGA1 Regulates IRS2 to Promote Inflammatory Responses and Oxidative Stress Injury in MPP-Induced cells.

Cell Biochem Biophys

Department of Neurology, The Second People's Hospital of Lianyungang, Lianyungang, 222006, Jiangsu Province, P. R. China.

Published: September 2024

Parkinson's disease (PD) is a prevalent neurodegenerative disorder for which novel treatment approaches are continuously sought. This study investigates the role of high-mobility group A1 (HMGA1) in modulating inflammatory responses and oxidative stress injury in PD. We utilized the murine dopaminergic neuronal cell line MN9D, treating cells with 1-methyl-4-phenylpyridinium ion (MPP) to mimic PD conditions. The expression levels of HMGA1 and insulin receptor substrate 2 (IRS2) were measured using quantitative polymerase chain reaction and Western blot assay. Cell damage was assessed with cell counting kit-8 and lactate dehydrogenase assays. Inflammatory response and oxidative stress were evaluated by quantifying interleukin (IL)-1β, IL-6, tumor necrosis factor-α, reactive oxygen species, superoxide dismutase, and malondialdehyde (MDA) levels using enzyme-linked immunosorbent assay and commercial kits. The binding interaction between HMGA1 and IRS2 was analyzed using chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. Our findings revealed that MPP treatment increased the expression of HMGA1 and IRS2. Downregulation of HMGA1 enhanced cell viability, reduced inflammation, and mitigated oxidative stress in MPP-induced cells. Further investigation demonstrated that HMGA1 bounded to the IRS2 promoter, enhancing IRS2 expression. Overexpression of IRS2 counteracted the protective effects of HMGA1 downregulation. In conclusion, HMGA1 exacerbates MPP-induced cell damage by activating IRS2 transcription, which in turn heightens inflammation and oxidative stress. These findings suggest that targeting HMGA1 could be a potential therapeutic strategy for PD.

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Source
http://dx.doi.org/10.1007/s12013-024-01510-7DOI Listing

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