Interferon Gamma Enhances Cytoprotective Pathways via Nrf2 and MnSOD Induction in Friedreich’s Ataxia Cells
نویسندگان
چکیده
Friedreich’s ataxia (FRDA) is a rare monogenic disease characterized by multisystem, slowly progressive degeneration. Because of the genetic defect in non-coding region FXN gene, FRDA cells exhibit severe deficit frataxin protein levels. Hence, pathophysiology plethora metabolic disruptions related to iron metabolism, mitochondrial homeostasis and oxidative stress. Importantly, an impairment antioxidant defences exacerbates damage. This appears closely associated with disablement key proteins, such as transcription factor nuclear erythroid 2-related 2 (Nrf2) superoxide dismutase (MnSOD). The cytokine interferon gamma (IFN-γ) has been shown increase expression improve functional deficits mice. Currently, IFN-γ represents potential therapy under clinical evaluation patients. Here, we show that induces rapid Nrf2 MnSOD different cell types, including patient-derived fibroblasts. Our data indicate signals two separate pathways enhance levels increased through early transcriptional regulation, whereas are induced post-transcriptional mechanism. We demonstrate treatment fibroblasts stimulates non-canonical activation pathway p21 potentiates responses exposure hydrogen peroxide. Moreover, significantly reduced sensitivity peroxide-induced death Collectively, these results presence multiple triggered therapeutic relevance FRDA.
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ژورنال
عنوان ژورنال: International Journal of Molecular Sciences
سال: 2023
ISSN: ['1661-6596', '1422-0067']
DOI: https://doi.org/10.3390/ijms241612687